EBMT annual conference continued this year, it was due to adopt a hybrid fashion, although the decision was made late on to take it solely online. This decision allowed Ukrainian refugees to take shelter within the proposed location. It is a decision that I am sure we can all agree is best served for the current horrific situation which is unfolding in Ukraine.
As always, we were in attendance, and we are here to give you our low down on what we thought may interest you!
Covid-19 is still very much in the picture, even if media outlets do not reflect it as avidly as in the past, and so the art of virtual conference once again resumed this year, allowing all to attend safely from home.
Unsurprisingly, the conference sparked interesting conversation amongst interesting guests from patient to health care professional. It highlighted how exciting the future is for Bone Marrow Transplantation and the avenues that could be explored in the near future to better the lives of patients from across the world.
BRAD & KATE – LIVING WITH GVHD
The most powerful messages within this community often come from those who have lived the experience. That is why Brad’s interesting and compelling story really caught our eye when looking through the programme. We couldn’t wait to see what he had to say on the topic of ‘Living with GVHD’ and he certainly delivered both interesting and town to earth information that left us all wondering… can more be done?
Brad’s story is both compelling and informative, the way he delivered the talk was engaging as he took us from diagnosis to today, it had us all hooked. Following a shock diagnosis of a rare form of T-Cell Lymphoma in February 2015, Brads cancer story began. It was originally thought he would not need treatment however soon enough develops found that rhetoric flipped, and Brad found himself beginning treatment in the form of chemotherapy. Sadly, the cancer only returned stronger which left a Bone Marrow Transplant the next option. Brad’s brother was found to be a clear 10/10 match and in November 2016 became his donor. From here, Brad’s story started…
GVHD
Following a successful transplant, Brad began to develop acute Graft Versus Host Disease. His symptoms were predominately eye pain, which originally was thought to be conjunctivitis. The reality did not pan out this way and unfortunately Brad soon lost all his vision. A diagnosis of GVHD was given and it left him and his partner Kate wondering what was next. Brad was still blind and faced a further four surgeries over the space of a year and half before he regained this.
The crux of Brads talk hit home as he dove into the realities of living with a disease like GVHD, and how him and his partner Kate have navigated that. It is something that he feels not enough is done, or known about and that became evident on their search for a health care professional to treat them. Both Kate and Brad highlighted how very few Health care professionals were experts on his condition which comes as a surprise when GVHD can be relatively common.
During the search for a solid treatment plan to manage Brads GVHD, Kate admitted she felt ‘powerless’ as his carer. It had been translated to her that Brad needed 24hour care, this is something any carer can appreciate the enormity of. Kate touched on the stress that this undoubtedly bought to her. We found the image below she shared most interesting, reflecting the very real life of a carer and every day worries you can feel as one.
As their talk continued a running similarity continued throughout. A message we received as – Education. Both Brad and Kate repeated continuously the need for more to be done to educate professionals on the importance of catching and treating GVHD as early as possible and how in doing so this will greater enhance the outcomes for patients who suffer from this disease. The pair admitted they did not want to see others go through the struggle of finding and locating the right treatment for the length they did.
This is why, both Kate and Brad have now released books on the topic. Brad, already a writer prior to this, released his book ‘Living With GVHD’ to make it the first of its kind in bringing to light the very real reality of living with such a disease following a battle with cancer. He proclaimed it his ‘journey’ opting away from the wording ‘battle’ whilst admitting there was no enemy to defeat and so he saw little reason in christening it with the name ‘battle’.
It is a book that we are sure will provide a lot of answers and support to many in a similar situation past and present.
Kate also took to paper, writing a memoir that she hopes will support those carers who find themselves in a situation her and Brad did just a handful of years ago.
‘Already Toast’ is a book designed to share the signs and symptoms of burnout to allow a caregiver to recognise their symptoms too. Often, we see that caregivers end up neglecting their own health to care for others and Kate agrees with this. Therefore, she has made it her mission to ensure that people feel connected, answered for and not alone in their personal lives through the help of this book.
Brad and Kates story really blew us away. It was both true, down to earth and thought provoking leaving us all wondering…can we do more?
ALAN is shocked and saddened by the events in Ukraine.
We stand in solidarity with the Ukrainian people, and with all those affected, particularly those who find themselves living with a cancer such as acute leukemia.
We are working with other networks to support blood cancer patients affected by the war.
A recent study published showed that patients with high-risk AML used both approach-oriented and avoidant coping strategies at the time of diagnosis, but that using more approach-oriented coping techniques was linked to less psychological distress and better quality of life. (Ref. Amonoo HL, Bodd MH, Reynolds MJ, et al. Coping strategies in patients with acute myeloid leukemia [published online ahead of print, 2021 Nov 12]. Blood Adv. doi: 10.1182/bloodadvances.2021005845.)
Sabatolimab, an immunotherapeutic therapy targeting TIM-3 on immune and myeloid cells, was well-tolerated and led to durable clinical responses when combined with hypomethylating agents in patients with very high/high-risk myelodysplastic syndrome and newly diagnosed AML. (Ref. Brunner AM, Esteve J, Porkka K, et al. Efficacy and Safety of Sabatolimab (MBG453) in Combination with Hypomethylating Agents (HMAs) in Patients (Pts) with Very High/High-Risk Myelodysplastic Syndrome (vHR/HR-MDS) and Acute Myeloid Leukemia (AML): Final Analysis from a Phase Ib Study. Abstract #244. Presented at the 2021 American Society of Hematology Annual Meeting, December 11, 2021.)
Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in AML and can be found in ∼20% of patients at diagnosis. A recent study analyzed a large cohort of patients with AML for the prevalence and prognostic impact of IDH mutations. A detailed analysis of different mutations revealed distinct clinical and comutational features of the IDH1-R132C mutation, and providing additional evidence in support of delineating the IDH2-R172K mutation as a distinct entity based on its comutational landscape and significant impact on outcome. The differences in outcome of distinct mutations of IDH must be considered in future trials. Our analysis serves as a benchmark for future studies incorporating novel agents to show improvements compared with conventional intensive regimens. (Ref. https://doi.org/10.1182/bloodadvances.2021004934)
Induction and consolidation therapy comprising venetoclax plus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) was highly effective for the treatment of newly diagnosed AML, according to research. (Ref. Lachowiez C, DiNardo CD, Takahashi K, et al. Venetoclax Combined with FLAG-IDA Induction and Consolidation in Newly Diagnosed Acute Myeloid Leukemia. Abstract #701. Presented at the 2021 American Society of Hematology Annual Meeting, December 13, 2021).
A combination regimen consisting of azacitidine with venetoclax and magrolimab showed clinical activity in older and high-risk patients with newly diagnosed AML. (Ref. Daver N, Konopleva M, Maiti A, et al. Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and Magrolimab (Magro) in Patients (pts) with Newly Diagnosed Older/Unfit or High-Risk Acute Myeloid Leukemia (AML) and Relapsed/Refractory (R/R) AML. Abstract #371. Presented at the 2021 American Society of Hematology Annual Meeting, December 12, 2021.)
Byrd et al report on the impact of PTPN11 mutations on AML mutational characteristics and patient outcomes for 1725 patients with AML. Patients with N-terminal SH2 domain PTPN11 mutations had an early death (<30 days) more often than those with phosphatase domain mutations. And PTPN11 mutations are associated with inferior outcomes in AML patients with wild-type NPM1.
Highlights include the higher co-occurrence of PTPN11 with NPM1, DNMT3A, STAG2 and inv3 mutations, the higher median number of (driver) mutations in PTPN11-mutated AML, and the adverse impact of N-terminal SHP2 domain PTPN11 mutations in certain contexts. (Ref. https://doi.org/10.1182/bloodadvances.2021006242)
MRD
Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in AML. However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization.
The treatment of ALL has evolved rapidly during the recent decade. The expanding use of modern sequencing techniques has elaborated the genetic background of ALL and helped to define new subtypes, such as Philadelphia chromosome–like subtype of B-cell ALL (Ph-like ALL). Novel immunotherapeutic approaches, such as bispecific T-cell engaging antibodies, antibody-drug conjugates, and chimeric antigen receptor T-cell therapy, have achieved encouraging results in relapsed or refractory ALL. In addition, other novel targeted therapies, such as the third generation tyrosine kinase inhibitor ponatinib and allosteric inhibitor asciminib are being introduced to Ph-like ALL and Ph+ ALL. Despite this progress, a significant fraction of adult patients still succumbs to leukemia or treatment-related events. Especially the treatment of elderly ALL patients remains challenging, as intensive chemotherapy regimens or allogeneic hematopoietic stem cell transplantation are frequently not suitable for nonfit patients. There is an urgent need for less toxic, yet effective treatment alternatives. A new study showed that the combination of ex vivo drug testing and molecular profiling is a powerful tool for identifying novel effective and actionable therapies for ALL patients. Targeting the apoptosis pathway by inhibiting antiapoptotic proteins (BCL2, BCL-XL, BCL-W) and p53 with BCL2 and MDM2 inhibitors in combination with established ALL drugs is a highly promising strategy for improving survival and reducing treatment-related toxicity. (Source: https://journals.lww.com/hemasphere/Fulltext/2022/03000/Targeting_Apoptosis_Pathways_With_BCL2_and_MDM2.8.aspx)
Wudhikarn et al present a retrospective analysis of combination blinatumomab and inotuzumab therapy in relapse/refractory adult acute lymphoblastic leukemia. The authors evaluate the impact of dual therapy on remission, relapse, and overall survival. They also provide outcome metrics for the subset of patients who proceeded to transplant following sequential therapy. These data are clinically relevant as the use of these medications to induce remission and potentially bridge to transplant continues to expand. Therefore, knowledge about response rates and toxicities will be valuable for clinicians and researchers alike. (Ref. https://doi.org/10.1182/bloodadvances.2021005978).
ADDITIONAL RESOURCES
Why patients with AML ≥60 years of age should or should not be offered early allogeneic stem cell transplantation ?
In a Point-Counterpoint discussion, the question of whether all patients over the age of 60 with acute myeloid leukemia (AML) should be offered an allogeneic transplant is discussed by experts in the field. Tey and Lane argue yes while Deeg argues no. What do you do in your practice? We hope that these articles will help you make an informed decision that greatly benefits your patients.
As announced in our previous News, 2 webinars were organised and hosted by Leukaemia Care to share the latest advances in acute leukemia and what it means for patients and their families:
Focus on AML
This webinar is aimed at patients and advocates to provide an overview of latest developments in the treatment of AML that were presented at the American Society of Hematology (ASH) Conference in Georgia, US, December 2021
Host / Moderator: Charlotte Martin, Leukaemia Care
Speaker: Dr Steve Knapper,
Dr Steven Knapper, Senior Lecturer and Honorary Consultant Hematologist at the University Hospital Wales
This webinar is aimed at patients and advocates to provide an overview of latest developments in the treatment of ALL that were presented at the American Society of Hematology (ASH) Conference in Georgia, US, December 2021.
Host / Moderator: Charlotte Martin, Leukaemia Care
Speaker: Tobias Menne, Newcastle University, Consultant Hematologist and Clinical Director for Research at Newcastle upon Tyne Hospitals NHS Foundation Trust.
From 10th to 14th December 2021, the Acute Leukemia Advocates Network (ALAN) virtually attended 62nd ASH Annual Meeting and Exposition.
On Friday 10th December, ALAN Chair, Zack Pemberton-Whiteley and ALAN Network Manager Samantha Nier gave an update to ALAN Members and Supporters on the 2021 plans and on planned 2022 activities. The meeting was very well attended, based on a good exchange and we are very happy with what we have been able to accomplish so far and are looking forward to achieving more in 2022. We are happy to share the presentation – just let us know by email at samantha@acuteleuk.org.
For acute leukemia, see below a list of sessions we thought were interesting – if you would like to report on one of these, please let us know.
-Satellite symposiums
Acute Myeloid Leukemia: Evidence-based guidance on current paradigms and new therapeutic approaches
Seizing opportunity in AML: how to realize the potential of novel therapeutics in diverse patient populations
The road to cures through immunotherapy and precision medicine
Adopting MRD assessment for hematologic malignancies in real-world settings: technique, role and utilization to improve patient outcomes
Asparaginase-based treatments in young and older adults with ALL: leveraging the pediatric experience
What clinicians want to know: addressing current questions and controversies in the management of AML and MDS.
Health Care Disparities in Blood and Marrow Transplantation: Issues and Potential Solutions
Advances in CAR-T Cell Therapy Across Hematologic Malignancies: From Pipeline to Clinical Practice
Unlocking the Benefits of CAR-T Therapy in Hematologic Malignancies: Latest Evidence and Practical Considerations for Delivering State-of-the-Art Care
–General sessions (Education / Scientific)
The COVID Crash: Lessons Learned from a World on Pause
Scientific Symposia on COVID-19 Vaccination in Immunocompromised Patients
ALL: New Directions for Adult Patients
AML: So Many Options, So Little Time
It Takes a Village: Maximizing Supportive Care and Minimizing Toxicity During Childhood Leukemia Therapy
ASH Clinical Practice Guidelines on AML in older adults
How Important Are in-Person Clinic Visits during Maintenance Therapy for Pediatric Acute Lymphoblastic Leukemia
AML Hospitalizations: Racial Disparity in Outcomes of Patients with Comorbidities
The ups and downs of therapy for children with Trisomy 21 and acute leukemia
How Can We Ensure That Everyone Who Needs A Transplant Can Get One?
Update in Graft vs Host Disease
-Other topics
Challenges and potential solutions to accelerate research; Regulatory perspective on data sharing and RWD to generate RWE; Patients viewpoint on real world data sharing; Clinical viewpoints on real world data for research
Novel Findings in CAR-T Cell Therapies for Hematologic Malignancies
Approved, but should we use it ? are the new trial designs effective ?
Pregnancy in Special Populations: Challenges and Solutions
AI, Data Science, Computer Vision and the Hematology Laboratory of the Future
Some videos
During the 63rd ASH Annual Meeting and Exposition, Know AML and Know ALL spoke with physicians to share their views on the latest advances and what it means for patients.
Do patients enrolled in clinical trials really represent the AML population? with Mycal Casey, Augusta University, Augusta, US.
Casey begins by discussing underrepresentation of Hispanic and African American populations as well as women in clinical trials. He goes on to outline the impact of mortality on clinical trials that lead to drug approval and global disparities in trial populations. Finally, Casey makes 3 suggestions that could improve the applicability of data and representation in clinical trials.
Should COVID-19 vaccination be postponed after AML therapy? with Sabine Haggenburg, Amsterdam UMC, Amsterdam, NL
Haggenburg begins by discussing COVID-19 risks to AML patients, and the responses to vaccinations that have been observed so far. However, she highlights that vaccination does not protect patients taking hypomethylating agents, such as azacitidine and decitabine.
How are advances in ALL genomics informing new treatment approaches? with Charles Mullighan, St. Jude Children’s Research Hospital, Memphis, US.
Mullighan begins by highlighting the impact advances in genomics have had on ALL diagnosis and treatment, such as RNA sequencing. He goes into more detail about subtypes and the shortcomings of a gene panel approach for ALL. Mullighan discusses the benefits for patients, such as improved risk stratification, and optimization of novel and conventional therapies. Finally, he highlights the value in tracking clonal mutations and outlines the role of genomics in T-ALL.
Why are novel TKIs needed for Philadelphia chromosome-positive ALL? What does this mean for patients? with Jorge Cortes, Augusta University, Augusta, US.
Cortes begins by explaining that despite a dramatic evolution in treatment, risks and outcomes for many patients can still improve. Cortes highlights hopes for better quality of life, higher cure rate, fewer toxicities, and reduced need for stem cell transplants. Finally, he discusses prospects for patients with Ph+ ALL.
Highlights
In collaboration with Leukaemia Care, we’ll be organising a series of webinars to reflect on ASH.
On October 9, the U.S. FDA placed a clinical hold on a trial assessing AstraZeneca’s AZD5991 in combination with venetoclax and as monotherapy for patients with relapsed or refractory AML. Source: BioSpace, October 21, 2021.
The U.S. FDA has placed a partial clinical hold on the phase Ib KOMET-001 study of Menin-KMT2A inhibitor KO-539 for the treatment of patients with relapsed or refractory AML. The agency’s decision follows a recent report by KO-539’s manufacturer, Kura Oncology, of a grade 5 serious adverse event resulting in a patient’s death. Source: Kura Oncology press release, November 24, 2021.
In an analysis of the phase III RATIFY trial published in Leukemia, researchers examined the molecular landscape of FLT3 internal tandem duplication (ITD) mutations in AML, confirming this subtype’s distinct heterogeneity and the negative prognostic impact of the tyrosine kinase domain-1 (TKD1) insertion site. The data also show that the negative impact of TKD1 insertions might not be overcome by treatment with the multikinase inhibitor midostaurin. This clinical observation “does not only confirm the known resistance to chemotherapy of patients with TKD1 insertions, but also to tyrosine kinase inhibitor (TKI) treatment, which is in line with preclinical data,”. (Ref. Rücker FG, Du L, Luck TJ, et al. Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results [published online ahead of print, 2021 Jul 28]. Leukemia. doi: 10.1038/s41375-021-01323-0).
A prospective study demonstrated that low dose decitabine + venetoclax is as safe and efficacious as maintenance therapy following allo-HSCT in patients with high-risk AML/MDS. There were no reported irreversible regimen-related toxicities. One important note is that the authors hypothesized that decitabine + venetoclax may influence the graft-versus-leukemia effect, though no evidence of this was observed, potentially due to the small sample size. Further investigation of this maintenance regimen in larger cohorts is required. (Ref. Wei Y, Xiong X, Li X, et al. Low-dose decitabine plus venetoclax is safe and effective as post-transplant maintenance therapy for high-risk acute myeloid leukemia and myelodysplastic syndrome. Cancer Sci. 2021;112(9):3636-3644. DOI: 1111/cas.15048).
What are the future prospects for FLT3 mutated AML?
Venetoclax with azacitidine (ven/aza) has emerged as a promising regimen for AML, with a high percentage of clinical remissions in newly diagnosed patients. However, approximately 30% of newly diagnosed and the majority of relapsed patients do not achieve remission with ven/aza. It was previously reported that ven/aza efficacy is based on eradication of AML stem cells through a mechanism involving inhibition of amino acid metabolism, a process which is required in primitive AML cells to drive oxidative phosphorylation. Herein we demonstrate that resistance to ven/aza occurs via up-regulation of fatty acid oxidation (FAO). Studies are needed to confirm inhibition of FAO as a therapeutic strategy to address ven/aza resistance. (https://pubmed.ncbi.nlm.nih.gov/33884374/)
A combination regimen consisting of azacitidine with venetoclax and magrolimab showed clinical activity in older and high-risk patients with newly diagnosed AML. (Ref. Daver N, Konopleva M, Maiti A, et al. Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and Magrolimab (Magro) in Patients (pts) with Newly Diagnosed Older/Unfit or High-Risk Acute Myeloid Leukemia (AML) and Relapsed/Refractory (R/R) AML. Abstract #371. Presented at the 2021 American Society of Hematology Annual Meeting, December 12, 2021. https://www.ashclinicalnews.org/on-location/ash-annual-meeting/azacitidine-venetoclax-magrolimab-shows-promise-newly-diagnosed-high-risk-aml/)
Sabatolimab, an immunotherapeutic therapy targeting TIM-3 on immune and myeloid cells, was well-tolerated and led to durable clinical responses when combined with hypomethylating agents in patients with very high/high-risk myelodysplastic syndrome (vHR/HR-MDS) and newly diagnosed AML. (Ref. Brunner AM, Esteve J, Porkka K, et al. Efficacy and Safety of Sabatolimab (MBG453) in Combination with Hypomethylating Agents (HMAs) in Patients (Pts) with Very High/High-Risk Myelodysplastic Syndrome (vHR/HR-MDS) and Acute Myeloid Leukemia (AML): Final Analysis from a Phase Ib Study. Abstract #244. Presented at the 2021 American Society of Hematology Annual Meeting, December 11, 2021. https://www.ashclinicalnews.org/on-location/ash-annual-meeting/sabatolimab-combined-hypomethylating-agents-appears-safe-effective-mds-aml/)
Induction and consolidation therapy comprising venetoclax plus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) was highly effective for the treatment of newly diagnosed AML, according to research. However, patients with AML harboring TP53 mutations had an inferior survival versus those with wild-type TP53 when treated with the combination. (Ref. Lachowiez C, DiNardo CD, Takahashi K, et al. Venetoclax Combined with FLAG-IDA Induction and Consolidation in Newly Diagnosed Acute Myeloid Leukemia. Abstract #701. Presented at the 2021 American Society of Hematology Annual Meeting, December 13, 2021. https://www.ashclinicalnews.org/on-location/ash-annual-meeting/venetoclax-plus-flag-ida-shows-promising-responses-newly-diagnosed-aml/)
Intensive chemotherapy regimens have been the mainstay of newly diagnosed AML induction therapy for several decades. During this time, alterations to the standard backbone therapy have yielded improved response rates, longer remissions, and improved survival in those who are fit and <60 years. Such regimens include the cladribine with higher dose cytarabine and idarubicin (CLIA) regimen which has been shown to achieve high complete response or partial response rates in a small study of patients with a mean age of 54. Further, the addition of the BCL2 inhibitor venetoclax, improves CR and PR rates in older patients (≥75 years) or unfit patients treated with a lower intensity treatment regimen using hypomethylating agents. In a recent study, it has been reported that the addition of venetoclax to the CLIA high intensity chemotherapy regimen resulted in durable complete responses in patients with newly diagnosed AML and high-risk MDS, with high rates of MRD-negativity. The authors considered that these data compared favorably with other published studies in similar patient groups without venetoclax. (Ref. Kadia TM, Reville PK, Borthakur G, et al.Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: A cohort from a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2021;8(8):e552-e561. DOI: 10.1016/S2352-3026(21)00192-7)
Poly(ADP‐ribose) polymerase 1 (PARP1) is a key mediator of various forms of DNA damage repair and plays an important role in the progression of several cancer types. The enzyme is activated by binding to DNA single-strand and double-strand breaks. Its contribution to chromatin remodeling makes PARP1 crucial for gene expression regulation. Inhibition of its activity with small molecules leads to the synthetic lethal effect by impeding DNA repair in the treatment of cancer cells. A recent study suggested that the positive correlation of PARP1, PARP2, PARP3, and TRPM2 genes in physiological cells, is disturbed in patients with AML and consequently, the need for further research of the mutual expression and regulation of different PARP family members is mandatory (ref. Gil-Kulik P, Dudzińska E, Padzikowska-Büchner E, et al. Different regulation of PARP1, PARP2, PARP3 and TRPM2 genes expression in acute myeloid leukemia cells. BMC Cancer. 2020; 20(1):435).
ALL
The U.S. FDA has approved CD19-directed chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel for the treatment of adult patients with relapsed or refractory B-cell precursor ALL. Source: FDA press release, October 1, 2021.
A retrospective study demonstrated that haploidentical HCT using posttransplant cyclophosphamide (PTCy) could be a preferred alternative donor HCT approach in adult patients with ALL, with superior OS . Although the OS was similar with haploidentical HCT compared to traditional MDS and MUD HCT, the risk of GvHD was reduced in the haploidentical HCT cohort. Further research aiming to prevent relapse, reduce death by infections, and establishing the role of haploidentical HCT using PTCy at different stages of ALL remission with a longer-term follow-up are warranted. (Ref. Wieduwilt MJ, Metheny L, Zhang M-J, et al. Haploidentical vs. sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia. Blood Adv. 2021;bloodadvances.2021004916. DOI: 1182/bloodadvances.2021004916)
APL
A recent study showed that patients with APL treated with ATRA-ATO reported better long-term quality of life outcomes than patients treated with chemotherapy. Also, late comorbidity and health problem prevalence was similar between patients with APL previously treated with ATRA-ATO or chemotherapy. The main objective of this study was to compare the long-term health-related quality of life of patients with APL treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) vs ATRA plus standard chemotherapy. Findings also suggest that, in the long term, the health status of patients with APL previously treated with ATRA-ATO may be comparable to that of the general population. (ref. Fabio Efficace et al. https://doi.org/10.1182/bloodadvances.2021004649)
MRD
Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in AML. However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement – full article here: https://journals.lww.com/hemasphere/Fulltext/2022/01000/Technical_Aspects_of_Flow_Cytometry_based.5.aspx
TP53 MUTATIONS
A single-cell multi-omic analysis of the genetic, cellular, and molecular landscape of TP53-driven transformation can provide unique insights into the evolution of chronic hematologic malignancies towards an aggressive acute leukemia. TP53 is the most commonly mutated gene in human cancer. Presence of “multi-hit” TP53 mutations is associated with lack of response to conventional treatments and poor outcomes, the authors explained. (Ref. Rodriguez-Meira A, Rahman H, Norfo R, et al. Single-cell multi-omics reveals the genetic, cellular and molecular landscape of TP53 mutated leukemic transformation in MPN. Abstract #9. Presented at the 2021 American Society of Hematology Annual Meeting, December 11, 2021.)
TRANSPLANTATIONS
How can venetoclax combinations be used in preparation for transplant?
OTHER TOPICS
Sociodemographic factors are associated with survival in acute leukaemia in studies across different countries. The potential causal links are multiple and suggest many relatively simple interventions that have received inadequate research and attention. Most clinical and scientific writing and discussion assume that a small number of biological factors should accurately predict outcome: cytogenetic and molecular genetic abnormalities, presenting white cell count and patient fitness for treatment. The reality is more complex.
Multiple sociodemographic factors affect outcomes and are inadequately addressed by the balance scale model. Consider ethnic differences—a recent study of over 25 000 adult AML patients in the United States demonstrated a 3-year survival of 34% in Black patients compared with 43% in White patients, despite no significant difference in baseline genetic risk categorisation and a “younger” median age in the Black patient group. Poverty has also been shown to strongly predict poorer outcomes in acute leukaemia. Limited English proficiency (LEP) describes people who are not fluent in spoken English but who will often speak other languages proficiently. Having LEP is associated with reduced survival in pancreatic cancer and higher risk of treatment failure in head and neck cancers. There are no published studies on LEP and acute leukaemia mortality, but a US study of Hispanic families in a paediatric stem cell transplant setting showed that parental LEP was significantly associated with prolonged hospitalisation.
Fundamentally, health systems and haemato-oncology departments have been mostly developed and operated by people with relative financial security, with advanced language proficiency and health literacy, and who are often from the majority ethnic group of their country. Even with the best intentions, we will not have sufficient collective imagination to address sociodemographic disparities until our practice is led and informed by people of varied ethnic, socioeconomic, and linguistic backgrounds. (Ref. Hibbs, Stephen, The Fragile Web of Care: Ethnicity, Poverty, and Language in Acute Leukaemia, HemaSphere: November 2021 – Volume 5 – Issue 11 – p e652, doi: 10.1097/HS9.0000000000000652)
Using technology to monitor outpatients undergoing cancer treatments at home was feasible and led to improvements in care, according to results of a pilot study. From January 2020 to August 2021, patients who were planning to start an intravenous anti-cancer treatment plan at Ochsner Health System, had an active patient portal account, and had a smart phone with the Ochsner portal application installed were asked to voluntarily participate in the Chemotherapy Care Companion program. The pilot program monitored patients’ vital signs to identify issues related to or exacerbated by their treatment. It is to be noted that This pilot study was limited by its requirements of smartphone access, basic technology skills, and collection of patient feedback, as well as its small sample size. (Ref: Pierce E, Stott C, Larned Z, et al. Ochsner Health System’s Chemotherapy Care Companion: Technology for monitoring outpatient Oncology patients at home. Clinical poster JL913. Presented at JADPRO Live Virtual, October 7-17, 2021.)
Grand rounds provide an opportunity for oncology advanced practitioners to discuss quality and safety across disciplines and may have positive effects on patient outcomes. This formal discussion group created a “new forum for oncology APs who were otherwise siloed within their own subspecialty. (Ref. Dryden C and Bazzell A. Oncology advanced practice provider quality and safety grand rounds: Development, implementation, and improving patient outcomes. Clinical poster JL914. Presented at JADPRO Live Virtual, October 7-17, 2021.)
The Acute Leukemia Advocates Network (ALAN) and Scientific Education Support (SES) are pleased to announce a strategic collaboration for patients with acute leukemias. The aim is to achieve improved disease awareness and education through initiatives using SES’ expertise in communications and medical education and utilising ALAN’s patient leadership in acute leukemias.
Both ALAN and SES have been providing disease awareness & medical education in the acute leukemia patient arena for several years and this has led to the establishing of a collaboration to strengthen initiatives for the benefit of the acute leukemia patient community.
The collaboration which will cover two key areas:
working together on new patient-focused disease awareness & educational initiatives in a range of acute leukemias involving medical information exchange and dissemination of best practice
SES will work with ALAN to deliver initiatives that support the ALAN Network members
The initial focus will be on raising awareness in acute lymphoblastic leukemia (ALL) through the launch of Know ALL.
Yvonne Ash, Managing Director of SES said: “We are delighted to be collaborating with ALAN and look forward to working together over the months and years ahead to provide additional support to the already highly effective acute leukemia patient community.
Mikis Euripides, Director of Patient Advocacy Programs at SES said “We pride ourselves on being patient-led, collaborative and informed by the latest science. We have been working with the leukemia patient community informally for several years across a range of hematological disease areas, and this collaboration will enable us to align our evidence-based patient led, educational strategies and activities more closely with ALAN’s goals”.
Zack Pemberton Whiteley, Chair of ALAN: “We are excited about entering into this collaboration to ensure the patient voice is heard across all acute leukemias, starting with the launch of Know ALL. ALAN is the global network for acute leukemia patient organisations and together with SES’ healthcare communications’ expertise, we believe this is a great opportunity.”
The Acute Leukemia Advocates Network (ALAN) is an independent global network of patient organisations, dedicated to changing outcomes of patients with acute leukemia by strengthening patient advocacy in that area. https://acuteleuk.org/
SES is a medical education provider, building healthcare professional and patient networks that facilitate open access science-driven, unbiased disease education through multichannel communications. https://scientificeducationsupport.com/
On 15th October, ALAN held its second (and virtual ) Acute Leukemia Global Summit.
Zack Pemberton-Whiteley, ALAN Chair welcomed attendees and opened the global summit, followed by Samantha Nier, ALAN Network Manager who gave an overview and status of ALAN’s activities.
Regional sessions reporting
Before the global summit, we met with groups from LATAM, from Middle East Africa and from Eastern and Western Europe to discuss projects, challenged faced, needs and all that is relevant to the region. These discussions were reported by our great speakers:
LATAM : Fernando Piotrowski, Executive Director ALMA (Argentina)
Middle East Africa: Bahija Gouimi, President and founder of AMAL Association (Morocco)
Eastern Europe: Mirjana Babamova, HEMA – Association for support of patients and caregivers of Hematology diseases (Macedonia)
Western Europe: Anne-Pierre Pickaert, Care4Access, representing Association Laurette Fugain (France)
Using evidence for advocacy impact
We then had a session on evidence-based advocacy with a training given by Zack Pemberton-Whiteley followed by concrete examples presented by various organisations and a panel discussion.
Zack Pemberton-Whiteley, Chair of ALAN and CEO of Leukaemia Care (UK)
Jana Pelouchova, Chair of Diagnoza Leukemie (Czech Republic), founder CML Advocates Network
Lauren Pretorius, CEO Campaigning for Cancer (South Africa)
Tracey Iraca, Executive Director MDS Alliance (USA)
We would like to thank all those participated in the summit !
With increasing diversity of advances in the treatment of AML, the need for anti-fungal prophylaxis against infection has also evolved. In the updated 2021 EHA guidelines, the recommendations are to follow the existing guidelines and where the evidence is limited, consideration should be given to individual patient factors and the clinical setting to decide on the appropriate antifungal agents. The risk of potential toxicity and drug-drug interaction in the specific patient population and whether a strong inhibitor is present should also be considered. (Ref Stemler J, Skoetz N, de Jonge N, et al. Antifungal prophylaxis in acute myeloid leukemia treated with novel agents. Oral abstract #S281. European Hematology Association 2021 Virtual Congress; Jun 11; Virtual https://library.ehaweb.org/eha/2021/eha2021-virtual-congress/324689/jannik.stemler.eha.guideline.antifungal. prophylaxis.in.acute.myeloid.leukemia.html)
A recent study shown that although the use of less-intensive therapies is associated with an increased risk of mortality in older patients with AML patients treated with these therapies also spend fewer days in the hospital. This study is the first step of reevaluating the role of intensity of therapy in AML and older patients that eventually could lead to improvement in the overall outcomes. It also highlights the importance of considering geriatric assessment for older patients with AML “to get a better sense of their overall health and not to rely on standard measures such as performance status scales or merely age”. (Ref: Sorror ML, Storer BE, Fathi AT, et al. Multi-site 11-year experience of less-intensive versus intensive therapies in acute myeloid leukemia. [published online ahead of print, 2021 Apr 28]. Blood. doi: 10.1182/blood.2020008812).
The use of combination chemotherapy, hypomethylating agents and/or hematopoietic stem cell transplantation are the current standard of treatment for AML. However, despite the many clinical benefits conferred by treatments for AML, health practitioners are facing challenges in managing associated toxicities that impact on the quality of life of patients. Treatment-related adverse events such as cardiotoxicity, hepatotoxicity, gastrointestinal toxicity, hematologic toxicity, immunological and pulmonary toxicity are common in patients with AML and contribute to treatment discontinuation and failure. Ravandi et al. provided updates on the phase III QUAZAR AML-001 trial, with a focus on onset of treatment-related gastrointestinal (GI) adverse events in older patients with AML in first remission receiving oral azacitidine, along with the toxicity management criteria. Awareness about the possibility for GI events during early oral azacitidine treatment will facilitate patients and clinicians to pre-plan and introduce prophylaxis and symptomatic interventions, which in turn will increase treatment adherence and better outcomes. (Ref. Ravandi F, Pocock C, Selleslag D, et al. Gastrointestinal events and management strategies for patients with acute myeloid leukemia in first remission receiving oral azacitidine (CC-486) maintenance therapy in the randomized, placebo-controlled, phase III QUAZAR® AML-001 trial. Presentation #1036. ASH 2020; Dec 5−8, 2020; Virtual)
A phase III study has recently shown that Oblimersen (G3139) can be safely added to conventional chemotherapy for older patients with AML. The addition of G3139 to chemotherapy failed to improve outcomes of older AML patients, but patients with secondary AML had improved disease-free survival. (Ref. Walker AR, Marcucci G, Yin J, et al. Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance). Blood Adv. 2021;5(13):2775-2787. DOI: 10.1182/bloodadvances.2021004233)
In a study presented at EHA2021 Virtual, adding short-term venetoclax to an intensive FLA-IDA chemotherapy regimen proved safe and led to high rates of overall response and MRD negativity in patients with relapsed/refractory AML. (Ref. Shahswar R, Beutel G, Gabdoulline R, et al. FLAVIDA chemotherapy induces MRD-negative remission in patients with relapsed/refractory acute myeloid leukemia. Abstract #S139. Presented at the EHA2021 Virtual Congress, June 9-17, 2021)
IDH1 inhibitor ivosidenib in combination with azacitidine, showed improved survival compared to azacitidine monotherapy for treatment of IDH1-mutated AML in global phase 3 trial AGILE.
In a small study of patients with IDH1-mutated myeloid malignancies, treatment with ivosidenib plus venetoclax, with or without azacitidine, had an acceptable safety profile and led to high rates of complete responses in patients with AML. (Ref. Lachowiez CA, Borthakur G, Loghavi S, et al. A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies. Abstract #7012. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021)
The FDA grants clearance for investigational new drug application for SYK inhibitor lanraplenib allowing for a phase I/II trial for combination therapy with FLT3 inhibitor gilteritinib in patients with R/R, FLT3-positive AML.
Less-intensive induction therapies are increasingly used in older patients with AML. Using an AML composite model. A study showed that in 2 cohorts, less-intensive therapies increased mortality in each of 3 risk groups defined by age, comorbidities, and cytogenetics. (Ref. https://doi.org/10.1182/blood.2020008812).
A recent trial showed that mutations in 7 genes independently predict overall survival in distinct cytogenetic groups of patients with AML aged ≥60 years and treated intensively. This led to report and validate a simple genetic model to identify older patients with AML with very good, intermediate, or poor outcome with 7 + 3. (Ref. https://doi.org/10.1182/blood.2021011103)
A novel tumor suppressor in AML called gene gamma GADD45g has been caracterized and shown to exert selective and potent antileukemic activities. GADD45g activation may be exploited therapeutically for treatment of FLT3-ITD+ and MLL-AF9+ AML by combining romidepsin with AC220 or JQ1. (Source: https://doi.org/10.1182/blood.2020008229)
First-in-Human study finds FF-10101-01 has clinical activity associated with high relapse and low survival/remission rates in relapsed/refactory FLT3-mutated AML. The findings of this early-phase study need to be confirmed in larger trials. (Ref. Levis MJ, Smith C, Perl AE, et al. Phase 1 first-in-human study of irreversible FLT3 inhibitor FF-10101-01 in relapsed or refractory acute myeloid leukemia. Abstract #7008. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021).
How could new treatment combinations improve outcomes in TP53 mutant AML?
How has acute myeloid leukemia treatment in elderly people changed in 2021?
Pediatric AML
Treatment outcomes for pediatric patients with AML have continued to lag behind outcomes reported for children with ALL, in part because of the heterogeneity of the disease, a paucity of targeted therapies, and the relatively slow development of immunotherapy compared with ALL. In addition, we have reached the limits of treatment intensity, and, even with outstanding supportive care, it is highly unlikely that further intensification of conventional chemotherapy alone will impact relapse rates. However, comprehensive genomic analyses and a more thorough characterization of the leukemic stem cell have provided insights that should lead to tailored and more effective therapies in the near future. In addition, new therapies are finally emerging, including the BCL-2 inhibitor venetoclax, CD33- and CD123-directed chimeric antigen receptor T-cell therapy, CD123-directed antibody therapy, and menin inhibitors. Here, we present 4 cases to illustrate some of the controversies regarding the optimal treatment of children with newly diagnosed or relapsed AML.
Transplantation
Hematopoietic stem cell transplant (HSCT) in patients with AML is often followed by maintenance therapy to prolong remission. Currently, there are no universally accepted standard maintenance therapies, leaving patients and physicians to determine which treatment to use by assessing the risk/benefit of the different options available. Manasee Shah and colleagues, investigated these preferences for post-HSCT treatment of AML using a discrete choice experiment. The study showed that there were differences between the attributes deemed to be important between patients and physicians when selecting post-HSCT maintenance therapy. Although both groups valued QoL, physicians valued duration of hospitalization less than patients, it also highlighted the importance of conversations between physicians and patients to fully understand patient treatment goals and preferences when determining the post-HSCT maintenance treatment. Acknowledging the differences between physician and patient treatment preferences will enable physicians to better select patient-centered treatments. (Ref. Zhou M, Yang H, Song Y, et al. Patient and physician preferences for post–hematopoietic stem cell transplantation maintenance treatment of acute myeloid leukemia. Oral abstract #S313. EHA2021; Jun 11, 2021; Virtual).
How are transplant options evolving for patients with ALL ?
MRD
In next-generation sequencing (NGS)-based MRD monitoring, the use of non-DNMT3A, TET2, or ASXL1 (non-DTA) mutations may predict relapse and survival following allogeneic hematopoietic cell transplantation (alloHCT) for patients with AML, according to findings published. (Ref. Heuser M, Heida B, Büttner K, et al. Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations. Blood Adv. 2021;5(9):2294-2304)
Patients with newly diagnosed AML treated with Ven+Aza who achieved CRc and an MRD response <10−3 had a longer DoR, EFS, and OS compared with those who did not achieve an MRD response (≥10−3). Higher rates of neutropenia were observed in patients that achieved an MRD response compared with those who did not. MRD response was also a significant predictor of OS, however, further studies are required to investigate the role of MRD response in clinical management. (Ref. Pratz KW, Jonas BA, Pullarkat V, et al. Measurable residual disease response in acute myeloid leukemia treated with venetoclax and azacitidine. Oral abstract #S137. European Hematology Association (EHA)2021 Virtual Congress; Jun 11, 2021; Virtual).
NGS has shown reliability in the detection of specific mutations at both time of diagnosis and complete remission in patients with AML. However, NGS-based MRD detection, has its limitations related to sensitivity and specificity, and its inability to differentiate between residual and clonal hematopoiesis. There is limited evidence on the role of NGS-MRD in patients with AML receiving allogeneic hematopoietic cell transplantation(allo-HSCT). A recent shown that the prognostic impact of detectable mutations at each pre-specified time point was correlated to the conditioning intensity. Persistent mutations were associated with higher risks of relapse and mortality both at pre-HSCT and post-HSCT-1m, and there was an advantage of serial NGS-MRD monitoring after allo-HSCT. The practicality of NGS-MRD monitoring will enable future studies investigating the feasibility of MRD-based approaches to reduce relapse in patients with AML. (Ref. Kim HJ, Kim Y, Kang D, et al. Prognostic value of measurable residual disease monitoring by next-generation sequencing before and after allogeneic hematopoietic cell transplantation in acute myeloid leukemia. Blood Cancer J. 2021;11(6):109. DOI: 1038/s41408-021-00500-9)
ALL
In this video, Chiaretti discusses the feasibility of improving the results of a chemotherapy-free regimen with dasatinib for patients with newly diagnosed Ph+ ALL.
Despite the availability of novel therapies, clinical outcomes remain poor in the 10‒20% of pediatric and adolescent patients with B-cell acute lymphoblastic leukemia (B-ALL) who relapse after initial therapy. The autologous CART-cell therapy KTE-X19 is currently being evaluated for the treatment of children, adolescents, and adults with other B-cell malignancies. The phase I ZUMA-4 study (NCT02625480) is investigating KTE-X19 in pediatric and adolescent patients with R/R B-ALL, and the long-term results elicited that no dose-limiting toxicities were reported, and that reported AEs were consistent with those known to be associated with CAR T-cell therapy. The 40 mL dose of 1×106 CAR T cells/kg was shown to be the optimal formulation of KTE-X19 for the treatment of children and adolescents with R/R B-ALL, as this formulation was associated with an improved safety profile compared with the other dose formulations, while maintaining high rates of minimal residual disease negativity and CR + CRi rates in this patient population. Therefore, this dose was selected for the phase II ZUMA-4 trial, which is currently enrolling pediatric patients with R/R B-ALL. (Ref. Wayne AS. ZUMA-4 phase 1 long-term results: KTE-X19 chimeric antigen receptor T-cell therapy in pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia. E-Poster #EP341. 26th European Hematology Association Annual Congress; Jun 11, 2021; Virtual).
How are transplant options evolving for patients with ALL?
Asparaginase Erwinia chrysanthemi (recombinant)-rywn has been approved by the FDA as part of a treatment regimen for adult and pediatric patients with ALL who have developed hypersensitivity to E. coli-derived asparaginase. Source: FDA press release, June 30, 2021.
A recent study showed that genomic testing leads to improved risk assignment in most adult patients with BCR-ABL1− B-ALL and antigen profiles affect outcome in B-ALL when considered in conjunction with genomic subtype. This prognostic importance of genomic analyses, which may translate into future therapeutic benefits. (Ref. https://doi.org/10.1182/blood.2020010144)
APL
APL is a subtype of AML involving complex coagulopathy resulting in early mortality due to hemorrhagic events. Currently, all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) is used as a frontline treatment in low-risk APL patients with excellent cure rates. The use of ATRA with ATO for high-risk APL patients is also under investigation. Despite the benefits offered by ATRA + ATO therapy, there are reports of varicella-zoster virus (VZV)—the causative agent of herpes zoster (HZ)—reactivation in APL patients treated with ATO.
There is a variety of effective therapeutic agents in use to treat AML where each one of them has a distinctive mechanism of action and unique toxicity profile. However, awareness about the impact of adverse events of any treatment, and knowledge about the extent to which a patient can bear the treatment, allows to maintain a balance between prolonging survival and the quality of life of patients.
Strategies to stimulate normal production of CD4+ T cells and/or balance Tregs during the first 6 months of ATO therapy are needed to effectively control herpes zoster reactivation risk. (Ref. Glass JL, Derkach A, Hilden P. Arsenic trioxide therapy predisposes to herpes zoster reactivation despite minimally myelosuppressive therapy. Leuk Res. 2021;106:106569. DOI: 1016/j.leukres.2021.106569)
Despite therapeutic advances, early death (ED) remains a major factor curtailing survival of APL. A recent study showed that early death after hospital admission remains one of the major determinants of outcome in APL in the modern era and that delays in administration of ATRA and hypofibrinogenemia are major predictors of early death. (Ref. https://doi.org/10.1182/bloodadvances.2021004789)
COVID-19 and Vaccination
In an amendment to its emergency use authorization for the Pfizer-BioNTech and Moderna COVID-19 vaccines, the U.S. FDA authorized a third dose of the shots for certain immunocompromised individuals.
People who have received solid organ transplants or who are considered to have an equivalent level of immunocompromise due to medical conditions are especially vulnerable to severe COVID-19 infection and may not have gotten adequate protection from the two-dose vaccine regimen. The FDA determined that a third dose may increase protection in these patients, but recommends they continue physical precautions to prevent infection. Those who are eligible for a booster shot are authorized to receive a third dose at least 28 days following the two-dose regimen of the same vaccine.
Infection with SARS-CoV-2 can be severe in patients receiving stem cell transplants especially for allo-HSCT recipients with a fatality rate of almost 30% in this group. In addition, severity of COVID-19 was linked to history of Grade 2–4 aGvHD and immunosuppression therapy.
In terms of vaccination, both vaccines examined in patients undergoing HSCT appear to be well tolerated with no new safety signals being recorded following at least one dose of the vaccination. There was an incidence of 9.7% of new cases of chronic GvHD and a low rate of worsening chronic GvHD symptoms (3.5%), though causality to the vaccines could not be established given the retrospective nature of the study.
While the efficacy of these vaccines remains unclear in this patient population, given the increased risk of severe or fatal COVID-19 in allo-HSCT recipients, vaccination is a good option for this group despite any potential activation of inflammatory pathways and immune-related adverse events. Vaccination in patients receiving allo-HSCT is supported by recommendations from the American Society of Hematology, the National Comprehensive Cancer Network and the American Society for Transplantation and Cellular Therapy.
Sources:
Mushtaq MU, Shahzad M, Chaudhary SG, et al. Impact of SARS-CoV-2 in hematopoietic stem cell transplantation and chimeric antigen receptor T cell therapy recipients. Transplant Cell Ther. 2021. Online ahead of print. DOI: 1016/j.jtct.2021.07.005
Ali H, Ngo D, Aribi A, et al. Safety and tolerability of SARS-CoV-2 emergency-use authorized vaccines allogeneic hematopoietic stem cell transplant recipients. Transplant Cell Ther. Online ahead of print. DOI: 10.1016/j.jtct.2021.07.008
Acute leukemias and MDS
In patients with acute leukemias or myelodysplastic syndromes (MDS), those who underwent haploidentical relative hematopoietic cell transplantation (haploHCT) had higher rates of grade 3-4 graft-versus-host disease and mortality compared with those who underwent HCT with a matched unrelated donor (MUD), according to results recently published. These preliminary results would need to be investigated further. (Ref. Gooptu M, Romee R, St Martin A, et al. HLA Haploidentical versus matched unrelated donor transplants with post-transplant cyclophosphamide based prophylaxis. [published online ahead of print, 2021 Apr 13]. Blood. doi: 10.1182/blood.2021011281)
Open survey : Understanding patient’s burden, quality of life, and alignment of patient-reported outcome measures to capture changes in high-risk MDS/AML.
Patients with AML and their caregivers generally defer end-of-life (EOL) transfusion decisions to clinicians without participating in shared decision-making. This tendency may delay hospice admission in patients who would benefit from this care the most, according to a new study published. This research adds to a multitude of other studies suggesting hematologists struggle to navigate care decisions for patients and families at the EOL. We know patients with blood cancers are more likely than those with solid tumors to die in the hospital, spend time in an intensive care unit or emergency department near the EOL, or to receive chemotherapy in the last two weeks of life. Hematologic patients are also less likely to use hospice care services overall. (Ref. Cripe LD, Cottingham AH, Martin CE, Hoffmann ML, Sargent K, Baker LB. Bereaved informal caregivers rarely recall a relationship between transfusions and hospice in acute myeloid leukemia [published online ahead of print, 2021 Apr 29]. Am J Hosp Palliat Care. doi: 10.1177/10499091211013290)
Fertility preservation
Discussions about possible infertility in young patients with cancer should happen early, and often.
Chemotherapy, radiation, and hematopoietic cell transplantation (HCT) are essential treatment options for patients with hematologic malignancies, but these therapies often harm patients’ reproductive health and future fertility. Nevertheless, a survey of nearly 7,000 patients of reproductive age who were diagnosed with cancer found that more than half did not receive counseling about the risk of infertility associated with cancer treatments.
With recent treatment advances for many cancers, survival rates have improved. Patients are living longer after a cancer diagnosis and conversations about future fertility are now considered an essential part of patient management and survivorship care for young adults, adolescents, and even prepubertal children.
“Several studies have found that, when you ask young adult survivors of cancer what they worry about related to their health, infertility is often one of the top concerns.”
