Effect of Bone Marrow Hypoplasia Secondary to Reinduction Therapy for Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) on Outcomes after Blood and Marrow Transplantation (BMT).
Authors: Wojtaszczyk Julie A. , Hahn Theresa , Battiwalla Minoo , Baer Maria R. , Wang Eunice , Barcos Maurice , Bambach Barbara , Padmanabhan Swaminathan , Wetzler Meir , McCarthy Philip L. 
Published: October 2019

Abstract
Refractory AML and MDS are difficult diseases to manage, even with allogeneic BMT, due to recurrent disease. In an attempt to cytoreduce prior to BMT, but also avoid the toxicities associated with multiple reinduction attempts, we altered our treatment practice to offer allogeneic BMT while the patient is hypoplastic after reinduction therapy. We retrospectively reviewed 47 consecutive patients (22 males, 25 females; median age 47 years, range 6–68,) with AML (n=36) or MDS (n=11) who received a first related (n=23) or unrelated (n=24) allogeneic BMT between 4/1/2003 and 3/31/2006 at Roswell Park Cancer Institute to compare outcomes by pre-BMT disease status. Bone marrow hypoplasia post-reinduction therapy was defined as a particulate biopsy with <20% cellularity and <5% myeloblasts within 1 to 4 weeks before BMT. Fourteen patients met this definition and were compared to 33 patients who had untreated MDS or AML in CR (n=25) or were relapsed/primary induction failure (n=8). We analyzed the association of the following characteristics with hypoplasia post-reinduction/pre-BMT: diagnosis, conditioning regimen, donor relation, HLA-matching, KPS, stem cell source, donor-recipient gender matching, age, ejection fraction, DLCO, FEV1, and time from diagnosis to BMT. In the univariate analysis, KPS was the only significant factor associated with hypoplastic status at time of BMT with all hypoplastic patients having a KPS ≤80 pre-BMT (p=0.002). Patients who were transplanted while hypoplastic had shorter overall survival (OS) compared to non-hypoplastic patients (p=0.0088) and also had a trend toward shorter leukemia free survival (LFS) (p=0.0936). Additionally, patients with active disease at BMT had poorer OS than patients who were untreated or in CR, and patients who were hypoplastic fared worse than those with active disease (1 year OS was 54% vs. 69% vs. 30%; p=0.027). Multivariate analysis of OS used a Cox proportional hazards model with forward stepwise selection conditional on the likelihood ratio with p<0.05 to enter and p>0.10 to remove each factor from the model. Since KPS correlated with hypoplastic status, both factors could not be added into the model simultaneously. Factors that were considered in the first model: KPS (≥90 vs. ≤80), conditioning regimen (FluMel vs. BuC vs. CT vs. FluC), donor (related vs. unrelated), age at BMT (continuous), and FEV1 (continuous). KPS was the only significant predictor of OS (RR=20.5; 95% confidence interval 2.7, 156; p=0.004). Substituting hypoplastic (yes vs. no) for KPS in the model yielded hypoplastic as the only significant factor (RR=3.06; 95% CI 1.3, 7.38; p=0.013). This study demonstrates that patients transplanted with bone marrow hypoplastia secondary to reinduction therapy have a compromised performance status, but that a low KPS is a stronger predictor of poor LFS and OS. Reducing the intensity of the reinduction regimen may increase performance status at BMT and improve overall outcome post-transplant.