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.

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.

Childhood cancer in Uruguay: 1992-1994. Incidence and mortality.

BACKGROUND: The referral of all children with cancer in Uruguay to a single center affords the opportunity to generate population-based incidence and mortality rates in this developing country in Latin America. PROCEDURE: All incident cases of cancer in children, 0-14 years of age, were ascertained from a combination of three sources for the period January 1992-December 1994. Diagnoses were grouped according to the International Classification of Childhood Cancer. Information on the size and age distribution of the total population was obtained from national census records. Follow-up was undertaken until December 1999 to afford a minimum interval of 5 years and the determination of mortality rates. RESULTS: The average annual incidence was 133.6 cases of cancer per million children per year and the disease distribution was similar to that in industrialized countries, with the exception of a higher rate and younger age distribution for the Hodgkin disease. The overall age-standardized mortality rate from cancer in childhood, at 6.5 per 100,000, was approximately twice that in the United States and Canada. CONCLUSIONS: Basic indicators of development suggest that Uruguay is more akin to the countries of North America and Western Europe than to those in the developing world. An opportunity has been identified to improve the outcome for children with cancer in this country.