Cytopenia of Unknown Cause Post Allogeneic Stem Cell Transplant As a Predictor of Clinical Outcome
Authors: Oh Annie L. , Ghimire Krishna , Kalakota Nandini , Sweiss Karen , Patel Pritesh R. , Rondelli Damiano 
Published: October 2019

Abstract
Temporary or long-lasting decrease of one or more blood cell lineages following allogeneic hematopoietic stem cell transplant (allo-HSCT) can lead to increased morbidity and mortality. Post-transplant cytopenia is often secondary to drug toxicity, viral infections, graft versus host disease (GVHD), or relapse. Less is known about the significance of cytopenia of unknown cause. Here we retrospectively analyzed 91 consecutive adult patients (median age 46 years; range: 19-63) who had received allo-HSCT conditioned with myeloablative fludarabine/ I.V. busulfan at our institution. Diagnoses included: acute myeloid leukemia (AML) or myelodysplatic syndrome (MDS) (n=57), acute lymphoblastic leukemia (ALL) (n=15), chronic myeloid leukemia (CML) (n=9), non-Hodgkin lymphoma (NHL) (n=5), B cell chronic lymphocytic leukemia (B-CLL) (n=2), myelofibrosis (n=1), unclassified myeloproliferative neoplasms (MPN) (n=2). Stem cell source was granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) in 81, bone marrow in 8 and cord blood in 2 patients. Median follow up for the entire cohort was 20 months (range 1-162 months). Patients with cytopenia of unknown cause were identified if they had full donor chimerism, negative cytomegalovirus (CMV) by molecular analysis, no active infections, acute GVHD <grade II, no chronic GVHD, no drug myelotoxicity, and at least one of the following: transfusion dependence for greater than 2 weeks, absolute neutrophil count (ANC) <1.5 x109/L, hemoglobin <8.5 g/dl or platelets <50 x103/L . Of 91 patients, 28 (31%) did not have any cytopenia post transplant, 48 (53%) had cytopenia of known cause (GVHD, n=9; infection, n=11; drug, n=2; relapse, n=25; graft failure, n=1). The remaining 15 patients (16%) had cytopenia of unknown cause. Of these 15, 9 cases had neutropenia, 6 thrombocytopenia (4 requiring platelet transfusion) and 2 had anemia (1 requiring red blood cell transfusion). Only one blood lineage was decreased in 13 patients and 2 lineages in 2 patients. Median onset of cytopenia was 60 days (range: 30-360 days) and median duration of cytopenia was 14 days (range: 14-150 days). When we compared the group of patients with cytopenia of unknown cause to the one without any cytopenia, no differences in patient characteristics, donor type, CD34+ cell dose, or stem cell source were found. A log-rank analysis did not show significant differences in overall survival (OS) (p=0.08) or progression free survival (PFS) (p=0.2) between the two groups. However, patients with cytopenia of unknown cause more frequently developed subsequent acute GVHD (53% vs 25%, p=0.06) and had a significantly higher risk of death due to infection compared to patients without cytopenia (p=0.04). Our results suggest that patients with cytopenia of unknown cause after allo-HSCT may have a worse outcome possibly due to a higher risk of acute GVHD and infections. Further studies are warranted on larger multicenter or registry data to establish the prognostic role of post-transplant cytopenia.

Disclosures
No relevant conflicts of interest to declare.