Bevezetés: Az allogén vérképző őssejt-transzplantáció (tx) indikációja gyermekkorban a magas szövődményráta és a nem elhanyagolható halálozás miatt csak az életet veszélyeztető betegségekre korlátozódik. A csökkentett toxicitású kondícionáló kezelések bevezetése után célul tűztük ki az egyes a transzplantációs szövődmények, mint graft-versus-host betegség (GVHD), vírusreaktiváció és transzplantációhoz társult thromboticus microangiopathia (TA-TMA) időbeli és egymáshoz viszonyított előfordulásának és a különböző kondícionáló kezelések és a fenti transzplantációs szövődmények összefüggéseinek feltárását. Betegek és módszer: Prospektíven száz (8,5 ± 4,9 év) gyermeket vizsgáltunk, akik malignus (n = 54) és nem malignus alapbetegség (n = 46) miatt részesültek allogén tx-ban. A kondícionáló kezelés megkezdésétől monitoroztuk a korai szövődmények, így az akut GVHD, a vírusreaktivációk, a TA-TMA felléptét, illetve relapszus jelentkezését. Eredmények: A gyerekek kétharmadánál (67%) észleltünk legalább egy korai szövődményt a felsoroltak közül. A leggyakoribb transzplantációs szövődmény a vírusreaktiváció volt (50%). Akut GVHD a betegek 26%-ánál, a medián 31. (10.–174.) napon alakult ki. Az akut GVHD-s esetek 27%-a (7/26) zajlott súlyos (Grade III–IV) formában. A TA-TMA döntően enyhe volt, kizárólag ciclosporin adása során, más transzplantációs szövődményekhez társultan jelentkezett. A TA-TMA kialakulását 5/20 esetben GVHD, 5/20 esetben vírusreaktiváció, és 4/20 esetben vírusreaktiváció és GVHD is megelőzte. A súlyos szövődmények alacsony számával ellentétben a relapszusráta (22/54; 41%) magas volt. A vizsgált betegcsoport összesített túlélése medián 3,8 (1,3–6,5) év követési idő múltán 74%. A nem malignus betegség miatt transzplantált gyermekek összesített túlélése kiváló (43/46; 93,5%). Ezzel szemben a malignus csoportban a halálozási arány – a magas relapszusrátának megfelelően – (17/54, 31,5%) magas. Következtetés: A csökkentett toxicitású kondícionáló kezelések bevezetése óta a súlyos korai transzplantációs szövődmények száma alacsony. A TA-TMA döntően enyhe formában, vírusreaktivációhoz vagy GVHD-hoz társultan jelentkezett. A malignus alapbetegség esetén a halálozás fő oka a relapszusok magas száma.
Introduction: Pediatric allogeneic hematopoietic stem cell transplantation (HSCT) is associated with severe treatment-related complications, including mortality. Therefore, HSCT remains a therapeutic option for patients with life-threatening medical conditions. After the introduction of reduced toxicity conditioning regimen, we aimed to identify the interrelation and the time to development of early transplant-related complications, as graft-versus-host disease (GVHD), viral reactivations and transplantation-associated thrombotic microangiopathy (TA-TMA). At the same time we also aimed to analyze the role of different conditioning therapies in the development of these complications. Patients and methods: Hundred pediatric (age 8.5 ± 4.9 yrs) patients, treated with HSCT for malignant (N = 54) and non-malignant (N = 46) indications, have been enrolled in this prospective study. From the start of conditioning therapy, early transplant-related comlications, as acute GVHD, viral reactivations, and TA-TMA and the occurrence of relapse were monitored. Results: Two third of the patients (67%) developed at least one of the monitored early complications. The most frequent HSCT complication was viral reactivation (50%). Acute GVHD occurred in 26% of patients, on median day 31 (10–174). 27% of the acute GVHD cases (7/26) were graded as severe (Grade III–IV). In the majority of patients, TA-TMA remained mild, self-limiting, without any sign of organ damage, and occurred only during ciclosporin immunosuppression. TA-TMA was preceded by acute GVHD in 5 in 20, by viral reactivation in 5 in 20, or by both in 4 in 20 cases. In contrast to the low incidence of early HSCT-related complications, relapse rate (22/54; 41%) was high. Overall survival after a median 3.8 (1.3–6.5) year follow-up time was 74%. Overall survival was excellent (43/46; 93.5%) in non-malignant patients. On the contrary, in patients with malignant diseases, mortality rate (17/54, 31.5%) was high due to high relapse rate. Conclusions: Since the introduction of reduced toxicity conditioning regimen, the rate of severe HSCT-related complications is low. TA-TMA occurred typically in a mild form after GVHD and/or viral infection or reactivation. In patients with malignant conditions, mortality was driven by high relapse rate.
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