Reduced-Intensity Conditioning followed by Peripheral Blood Stem Cell Transplantation for Adult Patients with High-Risk Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT), however it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine/melphalan prior to allogeneic peripheral blood stem cell transplant between 6/14/02 and 6/15/07 at City of Hope. Indications for the RIC regimen were: 1) age 50 or older (42%), 2) compromised organ function (54%), or 3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 months for living patients. Both overall survival and disease-free survival at two years was 61.5%. Relapse incidence was 21.1% and non-relapse mortality was 21.5% at two years. cGVHD developed in 86% of evaluable patients. In this series, no significant correlations were made between outcomes and patient age, presence of Philadelphia chromosome, relatedness of donor source or prior HCT. These high survival rates for high-risk ALL patients following RIC HCT may offer a promising option for patients not eligible for a standard myeloablative transplant.

Idarubicin-intensified BUCY2 regimens may lower relapse rate and improve survival in patients undergoing allo-SCT for high-risk hematological malignancies: a retrospective analysis

“…[40][41] Only for patients with low disease burden at the time of transplant, either in a CR or with low WBC and % blasts, can OS and DFS at 2 years reach 61.5%. 42 Compared to these studies, the effectiveness of IDA-intensified conditioning regimen in our study achieved better outcome.…”

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

“…In an attempt to avoid the high NRM seen with MAC-SCT and to exploit the GVL effect, investigators have been exploring the role of reduced-intensity conditioning (RIC) regimens for adult ALL patients who are considered poor candidates for MAC-SCT [11][12][13][14][15][16][17]. However, the role of RIC-SCT in adult ALL remains unclear because the interpretation of transplantation outcome is mainly limited by the small number of patients, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of the criteria used to select patients for transplantation.…”

Reduced-intensity vs myeloablative conditioning allogeneic hematopoietic SCT for patients aged over 45 years with ALL in remission: a study from the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT)

“…Therefore, allo-SCT using reducedintensity conditioning (RIC) may provide opportunities to obtain a significant GVL effect, without the adverse effects of intense myeloablative preparative regimens. [14][15][16][17] Marks et al 18 reported no effect of conditioning intensity on TRM or relapse risk after RIC and MAC in 93 and 1428 Ph chromosome-negative ALL patients, respectively, in first or second CR and in patients 416 years of age who received allografts from siblings and unrelated donors. Mohty et al 19 reported no effect of conditioning intensity on leukemiafree survival after RIC and after MAC in 127 and 449 ALL patients, respectively, in first or second CR and in patients 445 years of age who received allografts from HLA-identical sibling donors and were followed up for a median period of 16 months.…”