M Al-Mahr

Allogeneic stem cell transplantation for patients with congenital amegakaryocytic thrombocytopenia (CAT).

Summary:Five patients with confirmed congenital amegakaryocytic thrombocytopenia (CAT) underwent stem cell transplantation (SCT) from HLA-matched related donors at King Faisal Specialist Hospital and Research Center (KFSHRC). The median age at SCT was 3.2 years (range, 0.4–5 years). Conditioning regimen consisted of busulfan (BU) 4 mg/kg p.o. for 4 days (total dose of 16 mg/kg), and cyclophosphamide (CY) 50 mg/kg once daily i.v. for 4 days (total dose of 200 mg/kg). Antithymocyte globulin (ATG) was given i.v. at a dose of 30 mg/kg for 4 days pre-SCT (total of 120 mg/kg); graft-versus-host disease (GVHD) prophylaxis was with cyclosporine and methotrexate. Four patients engrafted and are alive and transfusion independent with a median follow up time of 30 months (range, 16–45 months). One patient failed to engraft and underwent a second SCT 4 months later but died of respiratory failure. We conclude that the use of allogeneic SCT may be curative for such patients.

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

Summary: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.

Bone marrow transplantation from matched siblings in patients with Fanconi anemia utilizing low-dose cyclophosphamide, thoracoabdominal radiation and antithymocyte globulin

Nineteen patients with Fanconi anemia (FA) and bone marrow failure underwent bone marrow transplantation (BMT) from matched siblings. Median age at BMT was 8.7 years. Conditioning consisted of low-dose cyclophosphamide (CY 5 mg/kg × 4 days) and thoracoabdominal irradiation (TAI 400 cGy). Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) in 13 patients and CsA plus methotrexate in 6 patients. Antithymocyte globulin (ATG) was added in the pretransplant as well as the post-transplant period. All patients received high-dose acyclovir from day 2 pre-BMT to day 28 post BMT, and intravenous immunoglobulins (IVIG), 500 mg/kg weekly from day 7 pre-BMT to day 90 post BMT. No fungal prophylaxis was given. All patients engrafted, (median, 14 days for an absolute neutrophil count ⩾0.5 × 109/l; median, 37 days for platelet count ⩾20 × 109/l). Fourteen (74%) patients are alive with sustained engraftment and are transfusion independent. Three (16.6%) patients developed acute GVHD; none developed chronic GVHD. Five (26%) patients developed invasive fungal infections, and two (10%) developed fatal CMV disease. We believe the addition of ATG may have contributed to the increased incidence of severe life-threatening fungal and viral infections in our series. Bone Marrow Transplantation (2001) 27, 139–143.

Transfusion-dependent congenital dyserythropoietic anemia type I successfully treated with allogeneic stem cell transplantation

Until recently, therapy for patients with severe congenital dyserythropoietic anemia (CDA) has been limited to blood transfusions and chelation therapy. Three children with transfusion-dependent CDA type I underwent allogeneic stem cell transplantation (SCT) from matched sibling donors. Conditioning was with cyclophosphamide 50 mg/kg/day for 4 days, busulphan 4 mg/kg/day for 4 days, and antithymocyte globulin (ATG) 30 mg/kg for four doses pre-SCT. All patients engrafted and are alive, and transfusion independent. To our knowledge, this is the first report of successful SCT in the management of CDA type I.

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.

Allogeneic stem cell transplantation in patients with Fanconi's anemia and myelodysplasia or leukemia utilizing low-dose cyclophosphamide and total body irradiation

Summary:Five patients with confirmed Fanconis anemia (FA) and myelodysplasia and/or leukemia underwent stem cell transplantation (SCT) from related donors at KFSHRC. The median age at SCT was 12.6 year (range, 6.2–15 years). Conditioning regimen consisted of cyclophosphamide (CY) 5 mg/kg/day i.v. for 4 days, total body irradiation (TBI) 450 cGy in a single dose. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine and antithymocyte globulins (ATG). The median time to engraftment (defined as ANC⩾0.5 × 109/l) was 16 days (range, 12–26 days). The median time to a self-sustaining platelet count of ⩾20 × 109/l was 27 days (range, 12–40 days). All patients engrafted. Two patients developed acute GVHD; one of the gut (grade 3) and the other of the skin (grade 1), and one patient developed chronic GVHD of the liver. Four are alive and well with no evidence of the disease; one patient died of bacterial sepsis after controlling her GVHD and clearing her pulmonary aspergillosis and CMV infection. We conclude that the use of low-dose CY plus TBI in patients with FA and MDS/AML undergoing SCT is adequate; the regimen is well tolerated and may be curative for such patients.

Congenital sideroblastic anaemia successfully treated using allogeneic stem cell transplantation

Therapy for patients with congenital sideroblastic anaemia has been limited to blood transfusions and chelation. Three children with congenital sideroblastic anaemia (SA) who were blood transfusion dependent underwent stem cell transplantation (SCT) from matched sibling donors. Conditioning consisted of cyclophosphamide 50 mg/kg/d for 4 d, busulphan 4 mg/kg/d for 4 d and anti‐thymocyte globulin (ATG) 30 mg/kg for four doses pretransplant. Graft‐versus‐host disease (GVHD) prophylaxis was with cyclosporin A and methotrexate. All patients engrafted, and are alive and transfusion independent. SCT can be curative for patients with SA.

The outcome of children with acute myeloid leukemia (AML) post-allogeneic stem cell transplantation (SCT) is not improved by the addition of etoposide to the conditioning regimen.

Relapse remains a concern for children with AML undergoing allogeneic SCT, so in an effort to reduce the risk of relapse in these patients, we intensified our pre‐SCT preparation by adding etoposide to the standard busulfan and cyclophosphamide regimen.

Allogeneic BMT for infantile acute leukemia: what is the optimal conditioning regimen?

Bone Marrow Transplantation 2 Zambon M, Bull T, Sadler CJ et al. Molecular epidemiology of two consecutive outbreaks of parainfluenza 3 in a bone marrow transplant unit. J Clin Microbiol 1998; 36: 2289–2293. 3 Cortez KJ, Erdman DD, Peret TC et al. Outbreak of human parainfluenza virus 3 infections in a hematopoietic stem cell transplant population. J Infect Dis 2001; 184: 1093–1097. 4 Wendt CH, Weisdorf DJ, Jordan MC et al. Parainfluenza virus respiratory infection after bone marrow transplantation. New Engl J Med 1992; 326: 921–926. 5 Whimbey E, Vartivarian SE, Champlin RE et al. Parainfluenza virus infection in adult bone marrow transplant recipients. Eur J Clin Microbiol Infect Dis 1993; 12: 699–701.