Improved Outcomes in Diamond Blackfan Anemia Treated Via Stem Cell Transplantation Since the Year 2000.

Diamond Blackfan Anemia (DBA) is a rare disorder characterized by red cell aplasia, congenital anomalies and a predisposition to cancer. Corticosteroids and red cell transfusions are the mainstays of therapy. Hematopoietic stem cell transplantation (HSCT) is curative in DBA, however outcomes have been variable. Nonetheless, preliminary data suggest improvement in HSCT outcomes since the year 2000.

To compare the degree of HLA compatibility, pre-transplantation iron burden, and survival before and since the year 2000 in sibling and alternative donor HSCT recipients, in order to evaluate if enhanced HLA matching techniques along with improved control of pre-transplant iron burden contribute to improved outcomes.

The DBA Registry (DBAR) is a comprehensive database of patients with DBA who are enrolled after informed consent is obtained. The patients, their families, and their physicians complete a detailed questionnaire. A review of medical records and telephone interviews are performed to complete and clarify the information provided. Presence of iron burden prior to transplant was determined based upon fulfillment of any of the following criteria: 1) serum ferritin level > 2000 ng/mL within 2 months prior to HSCT, 2) liver iron concentration greater than 8 micrograms per gram, dry weight within 6 months prior to HSCT (measured by MR or biopsy), 3) liver histology from biopsy or autopsy within 6 months of HSCT demonstrating 3+ or greater hemosiderosis or any level of fibrosis.

As of August 11, 2009, 583 patients have been enrolled in the DBAR, with 55 having undergone an allogeneic sibling or alternative donor HSCT. The median age at HSCT for all patients was 7 years, 8 months; 7 years, 2 months versus 9 years, 8 months for the 32 sibling and 23 alternative donor HSCT, respectively. There were 8 sibling and 13 alternative donor HSCT done prior to the year 2000 compared to 24 and 10 HSCT performed since the year 2000, respectively.

Prior to 2000, 8 of 8 sibling HSCT performed were HLA matched, whereas since the year 2000, there were 19 complete and 1 partial HLA matched sibling HSCT done. HLA reports on 4 sibling HSCT were not available for review. There were 5 full and 7 partial matches amongst the alternative donor HSCT done prior to 2000 and 6 full and 2 partial matches since the year 2000. Prior to the year 2000 HLA typing was done by serologic typing alone or by serologic methods for Class I and molecular methods for Class II. HLA typing was done by molecular techniques after the year 2000.

Overall survival at 5 years for all patients is 56.6 ± 8.7%; 77.3 ± 8.3% for sibling HSCT and 31.5 ± 12.7% for alternative donor HSCT (p=0.012). For sibling HSCT done prior to 9 years of age survival is 90.0 ± 9.5% and for those older than 9 years of age is 70.0 ± 11.6% (p=0.007). Survival for all patients prior to 2000 and since 2000 is 47.1 ± 11.0% and 72.4 ± 9.3%, respectively (p=0.184). Survival for alternative donor HSCT is 23.1 ± 11.7% prior to 2000 and 85.7 ± 13.2% since 2000 (p=0.047).

From data which are available, there are no reported pre-2000 cases of sibling HSCT where absence of iron is documented. Two cases of sibling HSCT pre-2000 had known significant iron overload. One of these patients is the only fatality amongst sibling donor HSCT pre-2000. Post-2000, there were 3 cases of sibling HSCT with significant iron overload and 7 cases of proven absence of iron burden (data on remaining patients are pending). In the alternative donor HSCT pool prior to 2000, 5 of 13 had proven pre-HSCT iron overload and 1 without (data on remaining 7 patients are pending). Since the year 2000, of the alternative donor HSCT, there were 2 proven cases with iron overload and 2 with proven absence of iron burden (data on 6 remaining patients are pending). Overall survival at 5 years for patients without evidence of iron overload is 53.3 ± 18.6% and for those with iron overload pre-transplant is 38.5 ± 23.3 (p=0.97).

The best outcomes for stem cell transplantation in DBA patients occur when using HLA-matched sibling donors in younger patients. There has been a significant improvement in survival with alternative donor SCT since the year 2000 which may be a result of improved HLA matching techniques. There is a trend to improved survival with lower pre-transplant iron burden.

No relevant conflicts of interest to declare.