Factors affecting the outcome of related allogeneic hematopoietic cell transplantation in patients with Fanconi Anemia.

Hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi Anemia (FA), and it is generally accepted that these patients should receive low-intensity conditioning because of the underlying DNA repair defect in their cells. Outcomes for recipients of matched related HCT have generally been favorable, but only a few studies have scrutinized the factors that may affect the eventual outcome of these patients. This retrospective analysis of 94 pediatric patients with FA who underwent related HCT at King Faisal Specialist Hospital & Research Center was carried out to attempt to identify factors that may affect outcome. Results showed overall survival (OS) probabilities of 92.5%, 89%, and 86% at 1, 5, and 10 years, respectively. In univariate analysis, use of higher dose cyclophosphamide (CY) (60 mg/kg) conditioning was associated with a better 10-year OS than lower dose CY (20 mg/kg) conditioning (91% versus 82%, respectively; P = .035), and use of radiation-containing regimens was associated with a significantly lower 10-year OS than nonradiation regimens (76% versus 91%, respectively; P = .005). Of the 4 regimens used in this study, the fludarabine-based regimen was associated with the highest survival (95.2%; P = .034). The use of the higher dose CY (60 mg/kg) was associated with a significantly increased incidence of hemorrhagic cystitis (HC) (20% versus 5.6% respectively; P = .049). Three patients (3%) developed squamous cell carcinoma (2 oropharyngeal and 1 genitourinary), at 9.4, 5.4, and 13.3 years after HCT; 2 of them had radiation-containing conditioning. In conclusion, our data suggest that although using a higher dose CY (60 mg/kg) conditioning regimen may be associated with better survival, it is also associated with a significantly increased risk of HC. The addition of fludarabine to the low-dose CY (20 mg/kg) is associated with the best survival. On the other hand, radiation-containing regimens are associated with significantly lower survival.

The Saudi experience in fludarabine-based conditioning regimens in patients with Fanconi anemia undergoing stem cell transplantation: excellent outcome in recipients of matched related stem cells but not in recipients of unrelated cord blood stem cells.

Low-dose cyclophosphamide (CY) is now considered the backbone of many of the conditioning regimens used in patients with Fanconi anemia undergoing allogeneic stem cell transplantation (SCT). To reduce the risk of rejection and improve results, CY is usually used in combination with other agents/modalities, such as antithymocyte globulin (ATG), busulfan, radiation, and, more recently, fludarabine (Flu). In this study, we used a uniform Flu-based conditioning regimen (ie, CY, Flu, ATG) in 26 pediatric patients with Fanconi anemia undergoing SCT. The median patient age at the time of SCT was 7.8 years, and the stem cell source was an HLA-matched related donor in 19 patients and partially HLA-matched unrelated cord blood in 7 patients. The CY, Flu, ATG regimen was well tolerated overall, with a remarkably low incidence of graft-versus-host disease and hemorrhagic cystitis. All 19 patients in the matched related donor group engrafted and were alive and transfusion-independent at a median follow-up time of 19 months, compared with only 2 of 7 patients in the unrelated cord blood group. We conclude that the combination of CY, Flu, and ATG in the doses used in this study is well tolerated, and that the proclaimed positive effect of adding Flu to the conditioning regimens of patients with Fanconi anemia undergoing SCT is most pronounced in recipients of HLA-matched related transplants. Its value in unrelated cord blood transplantation probably depends on other factors, such as the degree of HLA matching and the cell dose.

Successful Treatment of Pediatric Acute Myeloid Leukemia Presenting with Hyperbilirubinemia Secondary to Myeloid Sarcoma: A Case Report.

Myeloid sarcoma (MS), a tumor consisting of myeloid blasts with or without maturation, occurs at anatomical sites other than the bone marrow. MS of the gastrointestinal tract presenting with jaundice in children is rare. We report the case of a 4-year-old boy with a 6-week history of symptoms of obstructive jaundice due to a peripancreatic mass compressing the common bile duct. Six weeks later, blasts were found in a peripheral smear prior to surgical biopsy; bone marrow evaluation and flow cytometry results led to a diagnosis of acute myeloid leukemia (AML) with MS. No further invasive testing or temporary drainage was performed. He was started on induction therapy with full therapeutic doses of cytarabine, dose reductions of etoposide, and escalating doses of daunorubicin. His liver enzymes normalized, and he completed subsequent cycles of chemotherapy with full doses. The abdominal ultrasound showed resolution of the mass after the second cycle of chemotherapy. He is currently in remission three years after completing therapy. AML-directed chemotherapy in patients with obstructive jaundice secondary to MS may be beneficial without requiring invasive testing or temporary drainage procedures. Daily follow-up is crucial for chemotherapy dose modifications. Management plans should be individualized according to the patient's clinical condition.

Outcome and prognostic factors of acute lymphoblastic leukemia in children at the National Cancer Institute, Egypt.

OBJECTIVE: To improve survival of children with acute lymphoblastic leukemia (ALL) in the authors' institute and to define significant prognostic factors. METHODS: This study included 154 children with newly diagnosed ALL below the age of 18 years during the period August 1, 1998, to December 31, 2000. All patients were treated according to the NCI, Cairo, Egypt, treatment protocol modified from study XIII for high-risk ALL of St. Jude Children's Research Hospital. RESULTS: B-cell precursor phenotype was encountered in 73.4% of patients, T-cell in 26.6%. According to NCI/Rome criteria for risk classification, 58.4% of patients were in the high-risk group (90% of T-lineage compared with 47% of B-lineage ALL, P < 0.001). Nine patients (5.8%) died during induction and 10 patients (6.5%) failed to achieve remission. With a median follow-up of 43 months, the 3-year disease-free survival and its probability at 5 years were 80 +/- 3.6% and 75.3 +/- 4%, respectively; the 3-year event-free survival and its probability at 5 years were 69 +/- 3.8% and 65.2 +/- 4%, respectively. B-cell precursor ALL had 5-year probabilities of disease-free survival and event-free survival of 80.5 +/- 4% and 71.8 +/- 4.5% compared with 60.2 +/- 8.6% and 46.7 +/- 8% for T-cell, respectively (P < 0.01, log-rank test). Prognostic factors that had a statistically significant unfavorable impact on survival by univariate analysis were age 10 years or more, central nervous system involvement, T-lineage phenotype, high-risk group, DNA index less than 1.16, and slow early response to treatment. By multivariate analysis, central nervous system involvement, high-risk group, and slow early response to treatment still had prognostic significance. Risk classification demonstrated prognostic significance for B-lineage but not T-lineage ALL. CONCLUSIONS: This treatment protocol was effective in improving ALL survival among patients at the authors' institute compared with previous trials, although the outcome remains lower than that in more industrialized countries. Prognostic factors defined in this study were similar to those identified by other cooperative groups.