Donor Types and Outcomes of Transplantation in Myelofibrosis: A CIBMTR Study.

We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peripheral blood grafts for chronic phase myelofibrosis, 38% recipients of haploidentical-HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)-HCTs were independently associated with superior overall survival (OS) in the first 3 months [reference MSD, haploidentical HR 5.80 (95% CI 2.52-13.35), matched unrelated HR 4.50 (95% CI 2.24-9.03), and mismatched unrelated HR 5.13 (95% CI 1.44-18.31), P<0.001]. This difference in OS aligns with lower graft failure with MSD [haploidentical HR 6.11 (95%CI 2.98-12.54), matched unrelated HR 2.33 (95%CI 1.20-4.51), mismatched unrelated HR 1.82 (95%CI 0.58-5.72). There was no significant difference in OS among haploidentical, matched unrelated, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months post-HCT, relapse, disease-free survival or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. While MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and matched unrelated donors. These results establish haploidentical-HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.

Racial, Ethnic and Socioeconomic Diversity and Outcomes of Patients with Graft-versus-Host Disease: A CIBMTR Analysis.

Socioeconomic status (SES) and race/ethnicity have been associated with outcomes of allogeneic hematopoietic cell transplantation (allo-HCT). Certain aspects of GVHD management such as the need for long term care, prolonged immunosuppressive treatment, and need for close follow up for complications may exacerbate disparities. Adults (≥ 18 years) reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent a first alloHCT for acute leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm between 2008 - 2018 were included. Endpoints for those developing GVHD included overall survival (OS), transplant related mortality (TRM), and disease relapse. Models were adjusted for patient and transplant related variables. A two-sided p-value < 0.01 was considered significant. Among the 14,825 allo-HCT recipients, 6,259 (42.2%) and 6,675 (45.0%) patients developed aGVHD and cGVHD, respectively. In patients with aGVHD, non-Hispanic Blacks had increased TRM (HR 1.50, 95% CI 1.24-1.83, p=0.0001) and overall mortality (HR 1.31, 1.14-1.50, p=0.0002) compared with non-Hispanic Whites, an association that disappeared when severity of aGVHD was included in the model. Lower SES was associated with increased risk of disease relapse (p=0.0016) but not OS or TRM. In patients who developed cGVHD, race and ethnicity were not associated with OS, TRM and disease relapse. However, the highest quartile of annual household income (≥ $80,000) had improved OS (HR 0.77, 0.69-0.85, p<0.0001) and reduced TRM (HR 0.86, 0.67-0.87, p<0.0001) compared with lowest quartile, adjusting for race and ethnicity. Race/ethnicity and SES are associated with outcomes after GVHD. Optimizing health care resources available to low SES patients and strategies to minimize the risk of severe GVHD in non-Hispanic Blacks may improve long-term outcomes.

Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission.

For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. Am. J. Hematol. 91:322-329, 2016. © 2015 Wiley Periodicals, Inc.

Acute Lymphoblastic Leukemia, Version 2.2015.

Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org.

Acute lymphoblastic leukemia.

The inaugural NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for acute lymphoblastic leukemia (ALL) were developed as a result of meetings convened by a multi-disciplinary panel of experts in 2011. These NCCN Guidelines provide recommendations on the diagnostic evaluation and workup for ALL, risk assessment, risk-stratified treatment approaches based on the Philadelphia chromosome status and age (adults vs. adolescents/young adults), assessment of minimal residual disease, and supportive care considerations. It is recommended that patients be treated at specialized centers with expertise in the management of ALL.