Matched-related allogeneic stem cell transplantation in Saudi patients with Fanconi anemia: 10 year's experience.

Allogeneic SCT is curative for bone marrow failure in Fanconi anemia (FA) patients but the optimal conditioning regimen is undetermined. We report here our experience with 56 FA patients who underwent allogeneic matched related SCT. The conditioning regimen varied according to time of SCT and disease status at SCT; 22 patients (group A) received Cy 20 mg/kg, thoraco-abdominal radiation and antithymocyte globulins (ATG); and 34 patients (group B) received Cy 60 mg/kg and ATG. Median time to engraftment was similar (14 days) in both groups. Hemorrhagic cystitis was significantly more common in group B. Overall survival and event-free survival of all patients were 85 and 78.3% respectively. For groups A and B respectively, overall survival was 72.5 and 96.9% (P=0.013); and event-free survival was 72.5 and 82.3% (P=0.3). The use of the nonradiation Cy/ATG regimen in matched related SCT for FA patients offers better overall and event-free survival.

Allogeneic stem cell transplantation in Fanconi anemia patients presenting with myelodysplasia and/or clonal abnormality: update on the Saudi experience.

In the literature, there is an abundance of promising data on the outcome of allogeneic stem cell transplantation (SCT) in patients with Fanconi anemia (FA); however, the data on the outcome of FA patients who present with myelodysplasia and/or abnormal clone are sketchy as the entity itself is a rare one, although, it is believed that the presence of any of these factors confers a worse prognosis on the outcome of the transplant. This is an update of our experience in 11 such patients who underwent SCT at King Faisal Specialist Hospital and Research Center; 10 from the matched and related donors and 1 from a partially matched unrelated cord blood unit; the conditioning was with the same regimen consisting of cyclophosphamide (total of 20 mg/kg), anti-thymocyte globulin (total dose 160 mg/kg of the equine product or 52 mg/kg of the rabbit product) and total-body irradiation at 450 cGy. Ten patients remain currently alive, well and with no evidence of disease, with a median follow-up of almost 4 years.

Stem cell transplantation for patients with Fanconi anemia with low-dose cyclophosphamide and antithymocyte globulins without the use of radiation therapy.

In all, 22 patients with confirmed Fanconi anemia (FA) underwent stem cell transplantation (SCT) from HLA-matched, related donors at KFSHRC. Median age at SCT was 7.6 years (range, 2.5-14.6 years). Conditioning regimen consisted of cyclophosphamide (CY) 15 mg/kg/day intravenously (i.v.) for 4 consecutive days, in addition to equine antithymocyte globulins (ATG) given i.v. at 40 mg/kg/day for four doses pre-SCT. No radiation therapy was given. For graft-versus-host disease prophylaxis, we used cyclosporin at the standard doses; ATG was added at 20 mg/kg/dose i.v. on days 2, 4, 6, 8, 10, and 12 post-SCT (total of six doses). All patients engrafted and are alive and transfusion independent with a median follow-up time of 20.2 months (range, 3.3-59 months). One patient however developed a decrease in her WBC and platelet count. Her work-up revealed slightly hypocellular bone marrow, and a series of chimerism studies over 1 year confirmed that she has stable mixed chimerism; she remains transfusion independent. We conclude that low-dose CY without radiation therapy can be used satisfactorily in the conditioning of patients with FA undergoing related SCT.

Unrelated cord blood transplantation in pediatric patients: a report from Saudi Arabia.

In unrelated cord blood (UCB) transplantation, survival has been shown to correlate with the degree of HLA matching. Thus, to extend transplant access to different ethnic backgrounds, many western UCB transplantation banks now encourage donation from non-Caucasians. Until recently, Saudi Arabia did not have a national UCB bank. In this study we report our experience in UCB transplantation in children using units procured from western cord blood banks. A total of 97 children underwent unrelated UCB transplantation at King Faisal Specialist Hospital and Research Center (KFSHRC), of which 95 were of Arab ethnicity. A total of 30 patients had malignant disorders, 25 patients had non-malignant hematological disorders and 42 patients had inborn errors. Conditioning was according to disease, with six patients receiving reduced-intensity regimens. In all, 46 patients received one-Ag-mismatched units and 51 received two-Ag-mismatched units. Engraftment occurred in 93% of patients, the 100-TRM was 15%, acute GVHD developed in 20% of patients and chronic GVHD occurred in 9% of patients. The 5-year OS and EFS estimates were 52 and 43%, respectively. The search for UCB transplantation units for Saudi patients in western banks yielded reasonably compatible units for our patients; the results are consistent with published data. Our data are encouraging for UCB transplant programs in countries in which there are no national UCB transplantation banks.

Hyperbaric oxygen should not be used in the management of hemorrhagic cystitis in patients with Fanconi anemia.

Hemorrhagic cystitis (HC) is a common complication after stem cell transplantation (SCT) that occurs more frequently in patients with Fanconi anemia (FA) because of hypersensitivity of their cells to the agents used in the preparation for SCT (chemo and radiation). Many HC cases respond to therapy with hyperhydration and maintenance of adequate platelet counts, but refractory cases may require additional measures such as the use of prostaglandins, alum, or hyperbaric oxygen (HBO). We report here an unusual complication to HBO therapy in a FA patient consisting of generalized edema mimicking capillary leak syndrome but with no pulmonary edema or ascites.

Allogeneic stem cell transplantation in a patient with dyskeratosis congenita after conditioning with low-dose cyclophosphamide and anti-thymocyte globulin.

Bone marrow failure is the major cause of early mortality in patients with dyskeratosis congenita (DC); early trials with conventional conditioning regimens were associated with remarkable chronic morbidity and mortality, and the optimal conditioning regimen for these patients remains undetermined. We report a case of a child afflicted with DC who underwent related full HLA-matched stem cell transplant (SCT) using a regimen of low dose cyclophosphamide and antithymocyte globulin (ATG). The regimen was well tolerated and associated with no significant short-term toxicity.