Bone marrow transplant using fludarabine-based reduced intensity conditioning regimen with in vivo T cell depletion in patients with Fanconi anemia.

FA is the most common cause of inherited BMF syndromes. The only cure for BMF in FA remains HSCT. Due to DNA instability in FA, RIC has been used to decrease immediate and late complications of HSCT. Most FA conditioning regimens in mismatched and unrelated donor transplants rely on TBI, which increases the risk of secondary malignancies. Most of the non-TBI conditioning regimens use an ex vivo T-cell depletion approach, but this is not feasible at all pediatric stem cell transplant programs. To evaluate the success of HSCT in patients with FA using non-TBI conditioning regimens with in vivo T-cell depletion approach. HSCT using non-TBI based conditioning was performed on two siblings with FA. The first sibling underwent matched unrelated donor transplant with a BM graft using fludarabine, alemtuzumab, busulfan, and cyclophosphamide conditioning and cyclosporine and mycophenolate as GVHD prophylaxis. The second sibling underwent MSD transplant with UCB and BM grafts using similar approach, but without busulfan and mycophenolate. Both siblings had engraftment without signs of acute or chronic GVHD. Acute post-transplant complications included brief viral reactivations. At last follow-up, both siblings continued to have full immune reconstitution with stable chimerism. Conditioning regimens without radiation and inclusion of alemtuzumab can lead to successful engraftment without development of GVHD and reduce risk of developing secondary neoplasms, even with unrelated donor transplants.

Patterns of subsequent malignancies after Hodgkin lymphoma in children and adults.

To evaluate the impact of reduced radiation and combined modality therapy (CMT) in the treatment of Hodgkin lymphoma, we assessed the risk of second malignant neoplasms (SMNs) in patients who received extended-field radiotherapy only and patients who underwent CMT. Among 404 patients treated at Yale during 1970-2004, the risk of solid SMNs was elevated in the radiotherapy only group (n = 198, median follow-up = 21·1 years) compared to the general population, with a standardized incidence ratio (SIR) of 1·85 [95% confidence interval (CI): 1·17-2·78]. No increase was observed in the CMT group (n = 206, median follow-up = 14·3 years), although potential differences in SMN risk were indicated across the age spectrum in subgroup analysis. Patients who received mustard-containing regimens had increased risks for haematological SMNs (SIR = 8·74) and all SMNs (SIR = 1·85). When the analysis was stratified by age at diagnosis, children (0-20 years) had a significantly higher risk of SMNs (SIR = 5·24, 95% CI: 2·26-10·33), regardless of the treatment received. These findings suggest that recent treatment options utilizing lower dose radiation and less intense alkylator chemotherapy might be associated with lower incidences of SMNs among adults but not necessarily children.