Unrelated Umbilical Cord Blood Transplant for Diamond-Blackfan Anemia

Background: Hematopoietic stem cell transplant (HSCT) is the only curative option for patients with Diamond-Blackfan anemia (DBA). However, many patients lack suitable related or unrelated bone marrow donors. Unrelated cord blood transplant (UCBT) has successfully been used to treat many diseases.  Advantages of cord blood include: increased likelihood of finding a suitable graft particularly for racial and ethnic minorities, rapid availability, lack of risk to the donor, decreased likelihood of transmitting infections, more permissive HLA mismatching and decreased incidence of graft versus host disease (GVHD). Here we describe a cohort of patients who underwent unrelated umbilical cord blood transplant (UCBT) for DBA at a single center.

Methods: All patients who underwent UCBT for a diagnosis of DBA from 1996 to 2011 at Duke University Medical Center were eligible for this retrospective analysis (n=6). Patients were diagnosed with DBA on the basis of pure red cell aplasia on bone marrow aspirate and when available by ribosomal mutation testing (n=3).  Descriptive analysis was used for measures of engraftment, GVHD and survival.

Results: Patients had a median age of 3.1 years (range: 2.5-20.3 years), 3 were male and all were caucasian.  Prior to UCBT, patients had a median of 34 (range, 6-230) red cell transfusions and a median ferritin level of 2213ng/ml (range, 319 – 3328 ng/ml). Five of six patients received busulfan (1mg/kg/dose x 16), cyclophosphamide (50mg/kg/dose x 4) and equine Anti-thymocyte globulin (30mg/kg/dose x 3). The most recent patient received fludarabine (30mg/m² x 5), melphalan (70mg/m² x 2), thiotepa (200mg/m² x 1), alemtuzumab (1mg/kg/dose x 3) and hydroxyurea (30mg/kg/day x 13). Patients were HLA matched at 4/6 (n=2), 5/6 (n=2) or 6/6 (n=2) using low resolution HLA-A and –B and high resolution –DRB1 typing.  Median total nucleated cell dose pre-cryopreservation was 9.33x10^7 cells/kg (range: 2.3-18.4x10^7 cells/kg). GVHD prophylaxis was cyclosporine and steroids. All patients engrafted neutrophils (median 22 days, range: 19-91 days) and platelets (50K, median 81 days, range: 41-215 days). Two patients experienced grade II-IV acute GVHD and one had extensive chronic GVHD. With a median follow up of 5.5 years (range: 2-14 years), 4 of 6 (67%) patients are alive and well, full donor chimeras, and free of transfusions.  One patient died at day 70 from veno-occlusive disease and the second died two years post-transplant from polyserositis, chronic gut GVHD and kidney failure. None of the 4 surviving patients suffer from any major chronic medical problems.

Conclusions: UCBT can successfully be used for the treatment of DBA if otherwise suitable donors are not available. Survival following UCBT is similar to those reported by CIBMTR following related and unrelated adult donor transplants for DBA.¹

1. Roy, V., et. al. BBMT, 2005, 11(8); 600