Impact of Patient and Donor Factors on Successful Hematopoietic Stem Cell Transplantation for Acute T-Cell Leukemia/Lymphoma Patients in an Underserved Minority Population

Introduction

Adult T-cell leukemia/lymphoma (ATLL) is a rare but aggressive hematologic malignancy that disproportionately affects minorities. As minorities are currently underrepresented in the National Marrow Donor Program (NMDP), there remain significant challenges in achieving successful long-term outcomes through allogeneic hematopoietic stem cell transplantation (HSCT). There is currently limited data describing barriers that can delay timely access to this potentially curative treatment modality in this patient population.In this single-center retrospective study, we aimed to analyze various patient and donor factors impacting time and ability to reach successful HSCT for ATLL patients in an underserved minority population.

Methods

We retrospectively analyzed ATLL patients who were HLA typed at Montefiore Medical Center, Bronx, NY between 2013 and 2023. Demographic, clinical, and donor data were collected for each patient, including information from the NMDP registry search. Time-to-event data was collected relative to diagnosis date and included time to treatment initiation, patient HLA typing, donor HLA typing, and transplantation. We used chi-square and Mann-Whitney U Test for hypothesis testing to compare variable differences between the transplanted and non-transplanted cohorts. Univariate regression of time to transplant was then performed, with non-transplanted patients censored at last follow-up.

Results

Forty-four ATLL patients were HLA typed, and 20 (45%) underwent HSCT. The mean age at diagnosis was 54 years (range 25-76), with 23 (52%) being male. Ethnically, 33 (75%) were non-Hispanic black, 10 (23%) Hispanic, and one (2%) Asian. Subtypes included 21 (48%) with acute type and 23 (52%) with lymphomatous type ATLL. ECOG performance status was 0 or 1 in 41 patients (95%). Insurance coverage included Medicaid (50%), private and Medicare (18% each), and emergency Medicaid (9%). Excluding those in active transplant evaluation, there were no significant demographic or disease feature differences between transplant and non-transplant groups.

The median time to chemotherapy was 14 days, recipient HLA typing was 49 days, donor HLA typing was 100 days, and time to transplant was 274 days. Regarding treatment response, 45% had no response, 36% achieved complete remission (CR), 18% partial remission, and 5% relapsed. In the transplant cohort, 65% achieved CR and 5% were refractory, compared to 10% CR and 75% refractory in non-transplanted patients (p<0.001). On univariate analysis, relapsed/refractory disease before transplant significantly reduced transplant likelihood (p<0.01; HR 0.06). In addition, patients with three or more treatment lines (p=0.01, HR 0.23), recipient HLA typing beyond the median time of 49 days (p<0.01, HR 0.27), and donor HLA typing beyond the median of 100 days (p<0.01, HR 0.08) were also associated with lower transplant likelihood.

When analyzing NMDP match quality, only 30% of patients (n=13) had at least one potential 8/8 match, and 11% (n=5) had more than one. The transplant cohort had fewer full match donors (20%) compared to the non-transplant cohort (40%), and NMDP match presence was not significantly associated with transplant likelihood (p=0.82, HR 0.88). Among transplanted patients, 70% (n=14) used related donors (8 haploidentical, 6 full matches), 25% used unrelated donors (80% mismatched), and one patient (5%) underwent autologous HSCT. Among those excluded from transplant, 50% did not have any donor, 45% had related donors, and 5% had an unrelated donor. Reasons for transplant ineligibility included disease progression (60%), performance status decline (25%), patient choice (10%), and lastly social issues (5%).

Conclusions

Our retrospective study found that treatment refractoriness and prolonged time to HLA typing substantially reduced the likelihood of successfully reaching transplantation, underscoring an urgent need to improve frontline treatments and to prioritize expeditious patient/donor HLA typing. Surprisingly, NMDP match quality did not significantly affect transplant likelihood. This finding may be attributed to advancements in transplant techniques such as the use of post-transplant cyclophosphamide and abatacept, allowing greater access to HSCT in this minority population historically unable to find suitable quality matched donors, and mitigating other demographic and social barriers.

Shastri:NACE & PeerView: Honoraria; Jassen: Consultancy; Gilead, Rigel, Kymera: Consultancy; Kymera: Research Funding; Ryvu therapeutics: Research Funding; Geron: Speakers Bureau. Konopleva:Precision Biosciences: Research Funding; Sanofi Aventis: Consultancy, Other: clinical trials, Research Funding; Redona: Consultancy; Sellas: Consultancy; Pfizer: Other: clinical trials; MEI Pharma: Consultancy, Research Funding; Legend Biotech: Consultancy; Reata Pharmaceutical: Other: IP; ImmunoGen: Research Funding; Menarini Group: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: clinical trials, Research Funding; Rafael Pharmaceutical: Research Funding; Janssen: Consultancy, Other: clinical trials; Immune Oncology: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: clinical trials, Research Funding; F. Hoffmann-LaRoche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dark Blue Therapeutics: Membership on an entity's Board of Directors or advisory committees; Cellectis: Other: Clinical Trials; Boehringer: Consultancy; Bakx Therapeutics: Membership on an entity's Board of Directors or advisory committees; Auxenion GmbH: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Other: clinical trials, Research Funding; Allogene: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: clinical trials, Research Funding; Vincerx: Consultancy, Membership on an entity's Board of Directors or advisory committees. Verma:Bakx: Current equity holder in publicly-traded company; Janssen: Honoraria; Stelexis: Honoraria; Eli Lilly: Research Funding; Curis: Research Funding; Medpacto: Research Funding; Incyte: Research Funding; BMS: Research Funding; prelude: Research Funding; Throws Exception: Current equity holder in publicly-traded company. Feldman:Stelexis: Consultancy.