Allogeneic hematopoietic stem cell transplantation from an alternative stem cell source in Fanconi anemia patients: analysis of 47 patients from a single institution.

We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15); group 2, unrelated cord blood (N = 17), and group 3, related non-sibling bone marrow (N = 15). Twenty-four patients (51%) had complete engraftment, which was not influenced by gender (P = 0.87), age (P = 0.45), dose of cyclophosphamide (P = 0.80), nucleated cell dose infused (P = 0.60), or use of anti-T serotherapy (P = 0.20). Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007) and use of a fludarabine-based conditioning regimen (P = 0.046). Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011) and degree of HLA disparity (P = 0.007). Intensity of mucositis (P = 0.50) and use of androgen prior to transplant had no influence on survival (P = 0.80). Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD were diagnosed in 47 and 23% of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38% at approximately 8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with < 25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present) seeking for a related non-sibling donor is highly recommended.

Allogeneic hematopoietic stem cell transplantation from an alternative stem cell source in Fanconi anemia patients: analysis of 47 patients from a single institution

We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15); group 2, unrelated cord blood (N = 17), and group 3, related non-sibling bone marrow (N = 15). Twenty-four patients (51 percent) had complete engraftment, which was not influenced by gender (P = 0.87), age (P = 0.45), dose of cyclophosphamide (P = 0.80), nucleated cell dose infused (P = 0.60), or use of anti-T serotherapy (P = 0.20). Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007) and use of a fludarabine-based conditioning regimen (P = 0.046). Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011) and degree of HLA disparity (P = 0.007). Intensity of mucositis (P = 0.50) and use of androgen prior to transplant had no influence on survival (P = 0.80). Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD were diagnosed in 47 and 23 percent of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38 percent at ~8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with <25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present) seeking for a related non-sibling donor is highly recommended.

Therapy for severe refractory acute graft-versus-host disease with basiliximab, a selective interleukin-2 receptor antagonist.

Basiliximab is a chimeric monoclonal antibody that binds to the alpha chain of IL-2R on activated cytotoxic T-cells, inhibiting lymphocyte proliferation. We report 34 patients with refractory acute GVHD (grade III-IV) who received basiliximab from December 1998 to October 2003. Adults received 40 mg weekly (2-3 doses) and children received half of this dose. Median age was 13 years. Twenty-five donors were unrelated. The stem cell source was bone marrow in 30 and cord blood in four. Complete responses were seen in 27/32 patients (84%) with skin, 12/25 (48%) with gut and 6/23 (26%) with liver GVHD. Median duration of response was 38 days (5-1103). Overall survival at 5 years was 20%. Eleven patients (32%) are alive. The main causes of death were CMV (n=4), fungus (n=6), sepsis (n=8), hemorrhage (n=2), and relapse (n=2). Graft-versus-host disease flares were observed in 14 patients (41%), half being rescued by other therapies. In conclusion, basiliximab was able to induce complete responses in patients with refractory acute GVHD. Prospective studies are necessary to evaluate the optimal treatment schedule.

Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemia.

Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen-matched related donors. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2-3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0.001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44-58) months and 16 (3-52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients.