Horan, John

Objective We observed that pediatric patients with B lymphoblastic leukemia which expressed CD36 at diagnosis seemed to have worse outcome than patients whose blasts did not. Here, we describe the patient, disease characteristics, pathological, molecular, and genetic features and outcomes of patients with CD36+ B-LL compared to patients with CD36− B-LL. Methods We retrospectively reviewed all flow cytometry reports from September 2008 to December 2015 to identify patients diagnosed at our institution with CD36 expression on B lymphoblasts. CD36− control patients were chosen from our leukemia database and matched 2:1 to CD36+ patients for National Cancer Institute (NCI) risk group at diagnosis. We reviewed diagnostic marrow slides for cytoplasmic granules and abstracted clinical data from patient charts. To identify underlying genetic abnormalities, clinical FISH testing and RNA sequencing was performed on 5 of our CD36+ patients, and RNA-seq data from the NIH Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL Expansion Phase 2 data set were examined. Results Twenty-five of 366 (6.83%) patients diagnosed at our institution in the study period had CD36+ blasts. With a median follow-up of 5.32 years, 5-year event-free survival (EFS) and overall survival (OS) were significantly worse for CD36+ patients compared to CD36− patients who were NCI Standard Risk at diagnosis (EFS: 60% ± 15.49 vs 95% ± 4.87, P = .016; OS: 90% ± 9.5 vs 100%, P = .019). NCI Standard Risk patients whose blasts were both CD36+ and had granules had the worst survival compared to CD36− patients without granules (EFS 25% ± 21.65 vs 95% ± 4.87, P = .0004). From our CD36+ patients and the TARGET database, we found 2 ABL2 mutations, 1 PDGFRB mutation, and 2 NRAS mutations. Conclusions For NCI Standard Risk patients, CD36 expression on B-lymphoblasts identifies patients with B-LL who have especially poor outcome. This may be due to underlying genetic abnormalities that may be amenable to targeted therapy.

Purpose Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.