Hematopoietic SCT in children with Griscelli syndrome: a single-center experience.

In total, 11 consecutive pediatric patients with Griscelli syndrome (GS) type 2, who received allogeneic hematopoietic SCT (aHSCT) at our center between 1993 and 2007, were reviewed. The median age at transplantation was 8.2 months (range, 4-36.3 months) and the median time from diagnosis to transplantation was 3.7 months (range, 1.4-19.5 months). Seven patients developed an accelerated phase and were treated with chemotherapy before transplantation. At the time of transplantation, all patients were in clinical remission. The source of grafts was matched-related marrows in eight patients and partially mismatched unrelated cords in three patients. All patients were engrafted at a median time of 15 days (range, 12-36 days). Grade I-II acute GVHD and veno-occlusive disease occurred in three and one patient, respectively. A total of 10 patients are now alive and disease free at a median of 4.8 years post-HSCT. The post transplant course was complicated by CMV infection in four patients. One patient died in remission from septic shock, 6 months after transplantation. Chimerism studies at the last contact are available for nine patients: six patients have complete donor chimerism and three have stable mixed chimerism. Early aHSCT from matched-related donors or unrelated cord blood for children with GS is feasible.

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.

Allogeneic stem cell transplantation in patients with ß-thalassemia: King Faisal specialist hospital and research centre experience.

From January 1998-July 2006, 62 stem cell transplantation (SCT) were performed on 60 patients with beta-thalassemia from HLA-related match donors. The overall survival (OS) and event free survival (EFS) for all patients were 94 and 77%. The outcome of allogeneic SCT in our experience is satisfactory with OS 92% and EFS 77%. Transplantation at a young age and when the disease is mild offers the best outcome. More advanced disease is associated with higher rate of rejection and severe graft versus host disease.

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 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.

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.

Second allogeneic bone marrow transplantation after myeloablative conditioning analysis of 43 cases from single institution.

Between March 1984 and December 1999, a total of 43 second related allogeneic BMT procedures after myeloablative conditioning were carried out in our institution, 37 following allogeneic, and 6 following autologous BMT. Thirty one patients were males (72%). At 1st BMT (BMT1), median age was 11.5 years (range, 0.16-45 years). BMT1 was carried out for the diagnosis of AML in 13 patients (30%), SAA in nine (21%), ALL in six (14%), CML in six (14%), immunodeficiency in three (7%), NHL in two, beta-thal in two, HD in one, Red cell aplasia in one. HLA matching status for allogeneic BMT1 was full match in 33, one antigen mismatch in two and haplo identical in two patients. Median age at the 2nd BMT (BMT2) was 14 years (range, 0.41-46.7 years). Indications for BMT2 were recurrent hematologic neoplasm in 23 patients (53%), primary graft failure in 12 (28%) and late graft failure in 8 (19%). Median time from BMT1 to recurrence of hematologic neoplasm or late graft failure was 10 months (range, 2.5- 88 months). Median BMT1 to BMT2 interval was 13 months (range, 1-107 months). For BMT2, the same donor was used in 29 patients, while 14 patients had alternate related donor (12 full match, 1-one Ag mismatch, 1 haplo identical). A different conditioning regimen was used in the majority of the patients (39, 91%). Radiation containing conditioning regimen were used mostly for patients previously conditioned with chemotherapy only for BMT1 and chemotherapy conditioning +/- ATG for those who received radiation containing conditioning at BMT1. Bone marrow was the stem cell source for all patients at BMT2 and all except three autologous peripheral stem cell transplantation patient at BMT1. Significant organ toxicity leading to procedure related death in 13 patients (30%) was observed after BMT2. At a median follow up of 36 months after BMT2, 22 patients (51%) are alive (20 free of disease, 2 with recurrent disease) with overall median survival of 47.5 (SD +/- 9) months. Univariate analysis of relevant clinical factors identified the following variables as the only statistically significant favorable prognostic factors for overall survival: BMT1-BMT2 interval of > or = 6 months (P=0.0007) and age at BMT2 < or = 10 years (P=0.041). The nature of underlying disease (neoplastic or non-neoplastic) was not statistically significant (P=0.23). There was no statistically significant difference in survival outcome of BMT2 using same donor vs. alternate related donor (P=0.51). Due to the relatively limited sample size, multivariate analysis was not attempted. This single institution study suggests that second allogeneic BMT after myeloblative conditioning has an acceptable treatment related morbidity/mortality and favorable outcome if performed at age < or = 10 years and with an interval of > or = 6 months after the first BMT. Additionally same donor can successfully be used for the second transplant with similar survival outcome to alternate donor.

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

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.

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

Five patients with confirmed Fanconi's 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 x 10(9)/l) was 16 days (range, 12-26 days). The median time to a self-sustaining platelet count of >/=20 x 10(9)/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.

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.

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.

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 x 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 > or =0.5 x 10(9)/l; median, 37 days for platelet count > or =20 x 10(9)/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.

Extramedullary myeloid tumors in children: the limited value of local treatment.

PURPOSE: To determine the incidence of extramedullary tumors (EMT) in Saudi Arabian children with acute myeloid leukemia, the factors associated with these tumors and the impact of local treatment on local tumor control, complete remission and survival rates. PATIENTS AND METHODS: One hundred children, median age 6 years, who received their primary treatment for acute myeloid leukemia at King Faisal Specialist Hospital and Research Center, from 1983 to 1997 were studied. EMT at diagnosis occurred in 18 (18%) patients at 25 sites. Meningeal leukemia, hepatosplenomegaly, lymph node enlargement, gingival hypertrophy, and cutaneous infiltration were not included in the definition of EMT. With these exclusions, children with EMT were younger than those without EMT (median age, 3.5 v. 7.5 years) and were more likely to have meningeal leukemia at diagnosis (33% v. 10%). The t(8;21) translocation was associated with a 47% EMT incidence compared with 23% without the translocation. Local radiation treatment was given to 16 of 25 (64%) EMT sites. RESULTS: The overall 5-year survival rate for all patients was 28%, and this was not significantly influenced by the drug regimen used, meningeal leukemia at diagnosis, the presence of the (8;21) translocation, M4 and M5 morphology combined, or EMT at diagnosis. Significant differences were observed in the 5-year survival rates for patients who underwent allogeneic bone marrow transplantation (52%; N = 37) and those who attained complete remission (CR) but did not undergo transplantation (21%; N = 44) and those who did not achieve complete remission with initial therapy (5%; N = 19). Systemic and local EMT CR was achieved in 17 of 18 patients with EMT, including 12 patients who underwent radiation treatment and 5 of 6 of those who did not. Isolated relapse was not seen at an EMT site and was not noted at any later stage of the disease. CONCLUSIONS: Permanent local control at sites of EMT was achieved in all patients who attained a bone marrow CR, whether or not the site was irradiated. Local radiation treatment of an EMT site did not appear to contribute to overall CR and survival rates. The use of radiation treatment should be conservative and limited to patients in whom there is a real and immediate threat to vision or renal function or when the spinal cord is compromised.

Molecular detection of acute lymphoblastic leukaemia in boys with testicular relapse.

AIMS: To determine the role of polymerase chain reaction (PCR) based minimal residual disease (MRD) detection of leukaemia specific DNA in testicular relapse in childhood acute lymphoblastic leukaemia. METHODS: DNA was obtained from archival testicular and bone marrow samples from boys with acute lymphoblastic leukaemia who relapsed in the testes. Overlapping DJH clone specific primers derived from clonal immunoglobulin heavy chain (IgH) gene rearrangement in each case were used to analyse testicular or bone marrow DNA. RESULTS: Histologically normal end of treatment testicular biopsies in the five patients in longterm remission were all MRD negative, but MRD positive in three of six boys with subsequent testicular relapse. Histologically normal bone marrow samples taken at the end of treatment were MRD negative in five of seven cases, but MRD positive in all cases at the time of isolated testicular relapse. Three boys with unilateral testicular relapse underwent unilateral orchidectomy, rather than bilateral testicular irradiation, as part of their treatment. Two of these boys were MRD positive in the histologically uninvolved testes, and both had subsequent relapses either in the testes or the bone marrow, while the MRD negative patient has not had a testicular relapse. CONCLUSIONS: The presence of MRD in testicular tissue can be assayed with a PCR based method to detect clone specific antigen receptor gene rearrangements. In this setting, PCR is more sensitive than conventional testicular histology for predicting clinical outcomes. MRD assays might be useful in the management of boys at the time of isolated testicular relapse, to confirm the presence of unilateral testicular disease.

Wilms tumor associated with polycythemia: case report and review of the literature.

PURPOSE AND METHODS: A case of polycythemia with a normal serum erythropoietin is described, which led to the diagnosis of Wilms tumor. The clinical features of the reported cases of Wilms tumor associated with polycythemia are reviewed. RESULTS: An asymptomatic 6-year-old boy with polycythemia, a normal serum erythropoietin, and no evidence of erythroid colony forming activity in his serum was found to have a Wilms tumor. After resection and chemotherapy, he has had no recurrence of either the polycythemia or the Wilms tumor. There have now been 10 cases of Wilms tumor reported: 7 patients were more than 16 years of age, 8 were boys, and 9 were clinical stage I with a favorable histology. CONCLUSIONS: Polycythemia is a rare manifestation of Wilms tumor that can occur in the absence of an elevated serum erythropoietin and has an association with male gender, older patient age, and low clinical stage. Children with unexplained polycythemia should be investigated for Wilms tumor, even if the serum erythropoietin level is normal.

Prognostic significance of chemotherapy dosage characteristics in children with osteogenic sarcoma.

High-dose methotrexate (HDMTX), adriamycin (ADR), and cisplatinum (CDDP) are effective agents in the treatment of osteogenic sarcoma (OS). Individual patient doses are determined by prior successful clinical trials but may be reduced due to ongoing toxicities. It is unknown whether individualized dose reductions of these drugs influence disease outcome. We retrospectively studied 27 consecutively enrolled children treated with HDMTX, ADR, and CDDP as adjuvant chemotherapy for OS, for correlations between disease outcome and several characteristics of drug dosings the cumulative MTX, CDDP, and ADR doses administered and the mean MTX blood levels for each patient. With a median follow-up of 59 months, the actuarial overall and disease-free survival rates were 70% and 59%, respectively. Factors which favorably influenced prognosis on univariate analysis were a cumulative ADR dose of > 300 mg/m2 (P = 0.0002) and a cumulative MTX dose > 114 gm/m2 (P = 0.0048). By multivariate analysis only the cumulative ADR dose > 300 mg/m2 retained prognostic value. We conclude that adjuvant chemotherapy dosages may need to be adjusted for therapeutic efficacy in addition to adjustments made for toxicity. The effect of different cumulative HDMTX and ADR dosages on prognosis in osteosarcoma patients needs to be evaluated in a prospective trial.

Intestinal lymphangiectasia masquerading as coeliac disease.

Intestinal lymphangiectasia (IL) usually presents with either non-specific general or gastro-intestinal symptoms. As IL may mimic other gastro-intestinal disorders, the diagnosis is often delayed. Intestinal lymphangiectasia was diagnosed in three children who were originally treated as cases of coeliac disease. Two were sisters who had been placed on a gluten-free diet, for 3 years in one and 10 years in the other, with no favourable response. The third patient had been tried on various formulae and underwent many investigations for failure to thrive, oedema, abdominal distension and recurrent chest infections. The diagnosis of IL was based on clinical history, physical examination and radiological and histological findings. The three patients were commenced on a medium-chain triglyceride-based diet and vitamins, with satisfactory results.