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Introduction: HCT is the only curative option available in Brazil to SCD. Most patients do not have an unaffected Matched Sibling Donor (MSD), so alternative donor options are urgently needed. The Vanderbilt Global Haploidentical Learning Collaborative (VGC2) has led an international initiative to develop haploidentical HCT for SCD. Due to the 43% rejection rate with the original Hopkins protocol (Bolaños-Meade, 2012), Thiotepa (TT) was added with excellent results in adults, but 30% rejection in children (Kassim, 2024) despite marrow suppression with hypertransfusions and hydroxyurea. Objective: This paper is to report the experience of HCT in children and adolescents with SCD, comparing outcomes with MSD, haploidentical HCT as initially transplanted (Haplo) and Haplo with augmented conditioning therapy (AugHaplo). Methods: Conditioning therapy for MSD was (total doses) ATG 4.5 mg/kg, busulfan AUC 4.500 day, fludarabine (Flu) 120 mg/m2 and Cy 200 mg/kg, erythrocytheresis at admission to lower HbS < 20%‒30%. In all Haplo HCT, all patients had a mandatory prephase for at least 2-months with hydroxyurea 30 mg/kg/day, exchange transfusions to maintain HbS < 30% and reticulocytes < 10%. Haplo had ATG 4.5 mg/Kg, TT 10 mg/Kg, fludarabine 150 mg/m2, Cy 29 mg/Kg, TBI 200cGy, increased in the AugHaplo (Cy 50 mg/kg and TBI 400 cGy in a single fraction). GVHD prophylaxis: MSD CsA-Mtx and in all Haplos, PT-Cy, sirolimus, MMF. Results: From Sep 2016 to June 2024, 35 patients had HCT; 9 MSD and 13 Haplo, 13 AugHaplo. Median age was 11y (4‒20), 50% female. Among Haplos, donors were 4 siblings, 10 fathers, 10 mothers and 2 cousins; 83% sickle cell trait and all ABO-compatible. Main indications were: stroke or altered TCD/MoyaMoya (24); recurrent vasoocclusive crises (35); acute chest syndrome and priapism. Only one had anti-donor specific antibodies and was desensitized. All but 3 underwent exchange transfusions. The stem cell sources was marrow in 32/35; median CD34 7.5×106/kg (2.1‒11.2). Overall survival was 100%, event free survival 94% and median follow-up 20-months (0‒8 years). All patients engrafted (D+14-D+24). Rejection was so far avoided with low dose DLI in 2 Haplo with decreasing chimerism; 2 Haplo had 2ry graft failure on D+60 and D+180; 12 Aug-Haplo have 100% and 1 > 90% chimerism. Immunosuppression was suspended in 36% and is being reduced in 21%. 16% had III‒IV acute GVHD and 27% chronic GVHD, none severe. All patients had viral reactivations, mostly CMV and HHV6. Other complications in 1 patient each were Guillan-Barre syndrome, PRES, interstitial pneumonia and alveolar proteinosis secondary to sirolimus. Conclusions: All patients are alive. All 13 consecutive AugHaplo have > 90% chimerism. Viral reactivations are very frequent. Studies with larger cohorts and longer follow-up are needed to evaluate the long-term effects of this treatment strategy. |
