Malignant Infantile osteopetrosis. / Osteopetrosis infantil maligna.

INTRODUCTION: Malignant Infantile Osteopetrosis (MIOP) is a rare and severe genetic disorder due to abnormal osteoclast activity. OBJECTIVE: To report an infant who presented Malignant Infantile Osteopetrosis, reviewing the most relevant diagnostic and therapeutic aspects. CLINICAL CASE: A ten- month-old male infant with diagnosis of MIOP confirmed after presenting thrombocytopenia and visceromegaly. He was the first child of non-consanguineous parents, and among the findings, he presented severe hepatosplenomegaly, thrombocytopenia, and anemia; visual and hearing impair ment, and repeated infections. The diagnosis was confirmed by genetic study, which identified two heterozygous mutations in the TCIRG1 gene. Hematopoietic stem cells were transplanted without hematological recovery. The patient died due to occlusive venous disease. DISCUSSION: MIOP is a rare, severe, and early-onset disease, with a high rate of suspicion necessary in the presence of hepa- tosplenomegaly and bone marrow failure. Early diagnosis and hematopoietic stem cells transplanta tion are the only potentially therapeutic interventions of this lethal entity.

Haploidentical hematopoietic stem cell transplantation in children with high-risk hematologic malignancies: outcomes with two different strategies for GvHD prevention. Ex vivo T-cell depletion and post-transplant cyclophosphamide: 10 years of experience at a single center.

Forty patients with high-risk hematologic malignancies, median age 9 years, underwent haploidentical-HSCT from April 2005 to April 2015. Seventeen patients were transplanted with CD3-depleted PBSCs by negative selection (TCD group) following a reduced-intensity conditioning regimen (RIC), and 23 patients received T-cell-replete PBSCs followed by post-transplantation cyclophosphamide (PT-Cy group) after myeloablative conditioning (n=16) or RIC (n=7). Outcomes are reported for the TCD and PT-Cy recipients, respectively. Engraftment was achieved in 88% versus 100%. Median time to neutrophils>500/µL was 10 days versus 15 days. Platelets>20 000/µL occurred at a median of 16 days versus 20 days, respectively. Transplant-related mortality (TRM) was 24% versus 26% at 1 year. The cumulative incidence (CI) of grade III-IV acute GvHD was 7% versus 5%, and chronic GvHD 9% versus 53% (P=0.029). Relapse at 2 years was 31% versus 24%. Actuarial overall survival rates at 2 years were 47% versus 48%. Causes of death were infections (n=3), sinusoidal obstructive syndrome (n=4), acute GvHD (n=2) and relapse (n=9). These results indicate that haploidentical-HSCT is feasible in Uruguay. The TRM rate is of concern and should be the focus of continuing attention. Chronic GvHD risk was higher in the PT-Cy approach, so modifications are justified.

Successful treatment of metastatic retinoblastoma with high-dose chemotherapy and autologous stem cell rescue in South America.

High-dose chemotherapy (HDC) followed by autologous stem cell rescue (ASCR) is the only curative treatment for metastatic retinoblastoma, but its feasibility in developing countries is unknown. We report 11 consecutive children (six unilateral) treated in three South-American middle-income countries with HDC-ASCR. One patient had metastatic retinoblastoma at diagnosis and the remaining ones had a metastatic relapse. Metastatic sites included BM=6, bone=4, orbit=5 and central nervous system (CNS)=4. All patients received induction with conventional chemotherapy achieving CR at a median of 5.7 months from the diagnosis of metastasis. Conditioning regimens included carboplatin and etoposide with thiotepa in six or with CY in four or melphalan in one patient. All patients engrafted after G-CSF-mobilized peripheral blood ASCR and no toxic deaths occurred. Two children received post-ASCR CNS radiotherapy. Seven children have disease-free survival (median follow-up 39 months). CNS relapse, isolated (n=3) or with systemic relapse (n=1), occurring at a median of 7 months after ASCT was the most common event. In the same period, five children with metastatic retinoblastoma did not qualify for HDC-ASCR and died. We conclude that HDC-ASCR is a feasible and effective treatment for children with metastatic retinoblastoma in middle-income countries.

Feasibility and outcome of haploidentical SCT in pediatric high-risk hematologic malignancies and Fanconi anemia in Uruguay.

In total, 17 pediatric patients with hematologic malignancies (n=14) and Fanconi anemia (FA) (n=3) underwent haploidentical SCT with T-cell depletion. The patients were conditioned with reduced-intensity regimens, and CYA was used for GVHD prophylaxis. Successful engraftment occurred in 16 patients (94%). One patient failed to achieve a primary engraftment. Another patient rejected the first SCT after 10 weeks and had a successful second transplant. Of all engrafted patients, only one developed severe acute GVHD. Ten patients were alive at a median follow-up of 18 months (range, 5-62 months). The 5-years' OS was 53.8%. The three patients with FA are currently well with full-donor chimerism at 16, 6 and 5 months post transplant, respectively. The OS of 14 patients with high-risk hematologic malignancies was 47.6%. Three patients died as a result of post transplant leukemia relapse. CMV infection, GVHD and organ injury were other causes of mortality. Haploidentical SCT was found to be an alternative feasible treatment in Uruguay for patients who need allogenic transplantation but lack an HLA-identical family donor. It should be considered as an early option in FA patients before transformation or significant exposure to blood products.

Teicoplanin pharmacokinetics in pediatric patients.

BACKGROUND: The incidence of methicillin-resistant Gram-positive bacteria infections in febrile neutropenic children is high. Teicoplanin is an alternative treatment to vancomycin in these patients but few pharmacokinetic studies of teicoplanin in children have been conducted and optimal dosages have not been well-established. OBJECTIVES: To assess the pharmacokinetics of teicoplanin in combination with another antibiotic in Gram-positive infections in pediatric patients undergoing bone marrow transplantation and to determine the most appropriate dosage regimen for this type of patient. METHODS: We studied 21 patients divided into 2 groups. In Group A (n = 9) the dosage regimen consisted of 3 loading doses of 10 mg/kg at 12-h intervals, followed by a maintenance dosage of 10 mg/kg/day. Group B (n = 12) received the same loading dose and a maintenance dosage of 20 mg/kg/day. Plasma teicoplanin concentrations were monitored in all patients from the second day after the start of treatment and periodically thereafter. Serum concentrations above 10 mg/l were established as desirable trough values. RESULTS: In Group A trough values > 10 mg/l were not reached in five patients and treatment was modified owing to persistent fever. In Group B all patients attained trough values > 10 mg/l. Tolerance to treatment was excellent. CONCLUSION: In febrile neutropenic pediatric patients undergoing bone marrow transplantation, maintenance dosages of teicoplanin between 15 and 20 mg/kg/day assure serum concentrations above 10 mg/l. Dosages of 10 mg/kg/day do not assure serum through values above 10 mg/l.