A decision analysis of allogeneic hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission who have an HLA-matched sibling donor

Abstract

Clinical studies using genetic randomization cannot accurately answer whether adult patients with Philadelphia chromosomenegative acute lymphoblastic leukemia (ALL) who have a human leukocyte antigen (HLA)-matched sibling should undergo allogeneic hematopoietic stem cell transplantation (HSCT) or chemotherapy in first remission, as, in these studies, patients without a sibling donor undergo alternative donor transplantation or chemotherapy alone after a relapse. Therefore, we performed a decision analysis to identify the optimal strategy in this setting. Transition probabilities and utilities were estimated from prospective studies of the Japan Adult Leukemia Study Group, the database of the Japan Society for Hematopoietic Cell Transplantation and the literature. The primary outcome measure was the 10-year survival probability with or without quality of life (QOL) adjustments. Subgroup analyses were performed according to risk stratification on the basis of white blood cell count and cytogenetics, and according to age stratification. In analyses without QOL adjustments, allogeneic HSCT in first remission was superior in the whole population (48.3 vs 32.6%) and in all subgroups. With QOL adjustments, a similar tendency was conserved (44.9 vs 31.7% in the whole population). To improve the probability of long-term survival, allogeneic HSCT in first remission is recommended for patients who have an HLA-matched sibling.

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

“…This result appears to be conflicting with previous reports that show a superiority of allogeneic SCT over chemotherapy or autologous SCT. [44][45][46][47][48] In several studies, however, allogeneic SCT was offered to all suitable patients with a donor, whereas it was offered only to selected high-risk patients in the GRAALL trials. Of importance, differences in the high-risk ALL definition, which could include age or not, might also have an impact or even yield opposite conclusions.…”

Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT

“…[1][2][3][4][5][6][7] Traditionally, allogeneic HCT was performed using myeloablative conditioning regimens that incorporated high doses of TBI plus chemotherapy or a combination of BU and CY, among other options. 1,2,8,9 The resulting toxicity and consequent morbidity and mortality from the procedure, which exceeded 30% in most cases, limited the applicability of allo-HCT to patients of more advanced age or with a suboptimal performance status or a high HCT comorbidity index.…”

Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL)

“…These results with respect to relapse and survival seem to be comparable to those reported from larger studies, which mainly used TBI-based conditioning regimens with relapse rates between 24% and 61, and 5-year survival between 38 and 54%. [20][21][22][23] The TBI-containing myeloablative regimen developed at Stanford is considered the standard conditioning regimen for acute lymphoblastic leukemia; however, no randomized trials are available so far. Apart from acute toxicity, major concerns regarding TBI are long-term effects, such as secondary malignancies, which occurs more frequently after TBI-based regimens than after chemotherapy-based regimens.…”