Clinicohistologic Assessment of Bone Marrow Engraftment In Patients with Hematologic Malignancies Received Double Umbilical Cord Blood Transplantation – A Single Institutional Observation

Double umbilical cord blood transplantation (dUCBT) has been gradually accepted as an alternative for the treatment of patients with hematologic malignancy requiring allogeneic hematopoietic stem cell transplant but who lack suitable adult donors. The therapeutic strategy has achieved success with either reduced intensity conditioning (RIC) or myeloablative regimens (MAC). According to large series, the 3-year event free survival (EFS) and median overall survival (OS) for RIC-dUCBT approaches 39% and 45%, respectively. Nevertheless, early mortality and development of graft-versus host disease (GVHD) exist. In addition, since UCB contains 10-fold fewer hematopoietic stem cells (HSCs) than adult donor HSC sources, engraftment takes longer even with protracted or double dosage hematopoietic growth factor administration. The relationship between bone marrow (BM) status and delayed engraftment and survival in UCBT patients is not well illustrated. This study aims to retrospectively evaluate our institutional UCBT cases and correlate the bone marrow findings with the clinical outcome.

Clinical and pathologic data from patients with hematopoietic malignancies receiving dUCBT between 11/2009 and 05/2011 were reviewed. Sequential BM biopsies from each patient pre- and post- dUCBT were reviewed by two hematopathologists. BM cellularity and peripheral blood counts about day 21, 30, and 90 were correlated with CBCs, chimerism and the clinical outcomes as well as survival.

Thirty-one patients with hematologic malignancies (AML = 13, ALL = 6, CLL = 3, FL = 2, DLBCL = 2, HL = 1, MCL = 1, PTCL =1, Myeloma =1, and MDS = 1) received conditioning with chemotherapy and total body irradiation (MAC = 12; RIC = 19) followed by dUCBT. The median age was 45.7 years (range, 18–68 years) with a male to female ratio of 1.1:1. All patients received GvHD prophylaxis with cyclosporine and MMF and G-CSF from day +1 until engraftment. The median time to neutrophil engraftment was 22 days (range, 15 – 59) following MAC and 22 days (range 6 – 43) following RIC. Bone marrow cellularity, the corresponding WBC, and chimerism data are shown (Table 1). On the day 21 BM assessment, 80% (8/10) of patients receiving MAC achieved a marrow cellularity at or above the median and 87.5% (7/8) were alive at last follow-up. Following RIC, 59% (10/17) of patients achieved at least the median cellularity (10%) and 70% (7/10) survived. For patients below the median cellularity at day 21, survival was only 50% (1/2) and 43% (3/7) following MAC and RIC, respectively. With a median follow-up for survivors of 264 days (range 72 – 613) (MAC 286 days; RIC 239 days), the estimated overall survival at 1 year was 47% (28 – 68%). Thirteen patients died due to infection (n = 6), relapse (n = 3), GvHD (n = 2), or hemorrhage (n = 2).

Our results demonstrate that the bone marrow cellularity early post-transplant may serve as a predictor of survival following transplant. Since 6 of 13 patients (46%) died due to infection, this may indicate further impaired immune recovery regardless of total WBC. Larger case series are needed to elucidate a correlation between the bone marrow environment and the long term survival following dUBCT.

No relevant conflicts of interest to declare.