Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

Abstract

The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P 5 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P 5 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P 5 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634-641,

Impact of IKZF1 deletions on long-term outcomes of allo-SCT following imatinib-based chemotherapy in adult Philadelphia chromosome-positive ALL

“…Conditioning regimen and GVHD prophylaxis As previously described, 2,14,15,[32][33][34][35] all patients received SCT from a fully matched sibling or suitably matched (⩽ 2-allele mismatched) unrelated donor after completion of two courses of imatinibbased chemotherapy. A myeloablative conditioning regimen consisted of TBI (13.2 Gy) and CY (120 mg/kg).…”

PBSC vs BM grafts with myeloablative conditioning for unrelated donor transplantation in adults with high-risk ALL

“…[30][31][32][33][34][35][36] Subsequently, patients in CR received consolidation courses that consisted of high-dose cytarabine (2 g/m 2 , every 12 h, days 1-5) and mitoxantrone (12 mg/m 2 , days 1-2) therapy (at each odd cycle) alternating with the above induction regimens (at each even cycle), depending on donor availability and the time of transplantation. Central nervous system prophylaxis was performed by intrathecal administration of triple agents (MTX 12 mg, cytarabine 40 mg and methylprednisolone 50 mg; 6 times in total).…”

“…In addition, patients with Ph-positive ALL received imatinib-based chemotherapy before transplantation. [30][31][32][33]35,36 Transplantation procedures…”

“…GVHD prophylaxis was performed by administering tacrolimus plus MTX. [30][31][32][33][34][35][36] If residual leukemia was detected in the absence of GVHD at 3 months after transplantation, tacrolimus was rapidly discontinued.…”

What Is the Optimal Consolidation Strategy for Adult Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia Patients in First Complete Remission if You Are Not Able to Look for Minimal Residual Disease?

“…Allo-HCT using RIC regimens preserve the beneficial graftversus-leukemia effect while reducing the intensity and toxicity of preparative regimen. In general, MA and RIC regimens seem to be comparable in terms of efficacy in adult ALL patients especially in complete remission [39][40][41][42][43] .…”