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

Abstract

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 four years follow-up, incidence of relapse after HCT was 24% [95% C.I. 19-28] vs. 23% [95% C.I. 15-32] for the non-HCT (“chemo”) cohort (p=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort (HCT 37% [95% C.I. 31-42] vs. chemo 6% [95% C.I. 3 – 12], p<0.0001). DFS in the HCT cohort was 40% [95% C.I. 35-45] vs. 71% [95% C.I. 60-79] for chemo, p<0.0001. Similarly, OS favored chemo (HCT 45% [95% C.I. 40-50]) vs. chemo 73% [95% C.I. 63-81], p<0.0001). In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT (HR 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.

Phase 2 study of intensified chemotherapy and allogeneic hematopoietic stem cell transplantation for older patients with acute lymphoblastic leukemia

“…A recent analysis of patients up to age 50 compared a pediatric inspired non-transplant approach to that of allogeneic HCT, using data from Dana Farber ALL consortium and the Center for International Blood and Marrow Transplant (CIBMTR), and reported comparable survival and relapse rates. 38 In our study of older adults, despite a low TRM of 13%, no survival benefit was detected for HCT in older adults (65% versus 53% at 2 years, p-value 0.43; 42% versus 38% at 3 years). A previous study of intensified regimens in older patients did not assess the role of HCT, although two of their 51 studied patients, one Ph+ and one Ph-, did undergo HCT.…”

Allogeneic transplantation is not superior to chemotherapy in most patients over 40 years of age with Philadelphia‐negative acute lymphoblastic leukemia in first remission

“…These findings were later confirmed in an individual-patient-data meta-analysis that pooled results from 13 studies [22]. A recent report suggested that patients 18-50 years of age had better outcomes with a pediatric-inspired, non-HSCT approach (Dana-Farber Consortium pediatric-inspired protocol) as compared to patients that received chemotherapy followed by HSCT in first remission [24]. Most of the studies that prospectively assessed postremission chemotherapy vs. HSCT were conducted in younger patients as compared to our cohort and used only matched related donors and a myeloablative preparative regimen.…”

Advances in adult acute lymphoblastic leukemia therapy

“…In a recent retrospective analysis comparing 422 patients (18-50 years) having Ph-negative ALL who underwent alloHCT in first complete remission (CR) (as reported to the Center for International Blood and Marrow Transplantation Research [CIBMTR]) with 108 age-matched patients treated with the DFCI pediatric-inspired regimen, overall survival (OS) was better among patients who were treated with chemotherapy [51].…”