Cytogenetics Does Not Influence Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia

INTRODUCTION: Cytogenetics at diagnosis is the most powerful prognostic factor in acute lymphoblastic leukemia (ALL) patients treated with conventional chemotherapy. However, less is known about the prognostic significance of initial cytogenetics on patients who undergo allogeneic hematopoietic stem cell transplantation (alloHCT).

METHODS: The objective was to investigate the effect of cytogenetics, and other disease-/transplant-related factors, on leukemia-free survival (LFS), overall survival (OS), relapse incidence (RR) and non-relapse mortality (NRM) among adult ALL patients who undergo alloHCT. We retrospectively analyzed a consecutive case-series of 359 adult ALL alloHCT patients treated at the City of Hope from 09/2003 to 03/2014 (analytic date: 08/2014). Univariate Cox regression analyses (or competing risks analogue) were performed evaluating age at alloHCT, cytogenetic risk, leukemia phenotype (B vs. T), initial WBC count, disease status at alloHCT, stem cell source, conditioning intensity, donor type, and GVHD prophylaxis (tacrolimus/sirolimus (T/S)-based vs. others). Significant factors (p<0.10) by univariate analysis were included in the multivariable model.

RESULTS: The median age was 38 years (range: 18-72). The majority of patients (n=325; 91%) were B-cell, median WBC at diagnosis was 17x10³/mL. Cytogenetic risk at diagnosis was classified as good, intermediate, poor or unknown in 2%, 43%, 46% and 9%, respectively. Median time from diagnosis to alloHCT was 7 months (range: 2.2- 279.1). Disease status at alloHCT was CR1, CR2 and >CR2/refractory in 60%, 17% and 23% of cases, respectively. The source of stem cells was peripheral blood in 308 patients (86%). Donors were matched siblings in 193 patients (54%); conditioning regimen was myeloablative in 81%. T/S-based GVHD prophylaxis was used in 289 patients (81%). Median follow-up: 45 months (range: 3-128) in surviving patients; 3-year OS, LFS and RR estimates were 54%, 47% and 27%, respectively; one-year NRM was 19%.

By univariate analysis, cytogenetic risk, disease status at alloHCT, stem cell source and T/S usage were predictive for OS and LFS. In multivariable analyses, disease status at HCT and T/S usage were independent predictors for LFS [CR1 vs. CR2: HR = 1.69, p = 0.02; CR1 vs. others: HR = 2.94, p < 0.01; T/S vs. others: HR =1.5, p = 0.03] and OS [CR1 vs. CR2: HR = 1.89, p <0.01; CR1 vs. others: HR = 2.82, p < 0.01; T/S vs. others: HR =1.53, p = 0.04]. For RR, only disease status at HCT was found to be predictive [CR1 vs. CR2: HR = 2.17, P <0.01; CR1 vs. others: HR = 3.48, P<0.01]. Only T/S usage was associated with reduced NRM [T/S vs. others: HR =1.7, p = 0.04].

CONCLUSIO: Among adult ALL patients who underwent alloHCT, cytogenetics at diagnosis did not influence outcomes. However, non-CR1 status at HCT adversely affected OS, LFS and LR. Usage T/S based GVHD prophylaxis regimen was associated with improved OS, LFS and NRM.