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Terminal complement blockade by humanised monoclonal antibody eculizumab has been used to treat transplantation-associated thrombotic microangiopathy (TA-TMA) in recent years. This retrospective international study conducted by the Paediatric Diseases (PDWP) and Inborn Error Working Party (IEWP) of the European Society for Blood and Marrow Transplantation (EBMT) describes outcome and response of 82 paediatric patients from 29 centres who developed TA-TMA and were treated with eculizumab between January 2014 and May 2019. The median time from hematopoietic stem cell transplantation (HSCT) to TA-TMA manifestation was 92 days (range: 7-606) and from TA-TMA diagnosis to the start of eculizumab treatment 6 days (range: 0-135). Most patients received eculizumab weekly (72%, n = 55) with a standard weight (kg)-based dose (78%, n = 64). Six months from beginning of eculizumab therapy, the cumulative incidence of TA-TMA resolution was 36.6% (95% CI: 26.2-47) and the overall survival (OS) was 47.1% (95% CI: 35.9-57.5). All 43 patients with unresolved TA-TMA died. The cause of death was HSCT-related in 41 patients. This study also documents poor outcome of patients without aGvHD and their frequent concomitant viral infections. Considering recent publications, intensified eculizumab dosing and complement monitoring could potentially improve upon outcomes observed in this study.

Allogeneic hematopoietic stem cell transplantation (HSCT) has become a standard part of therapy for a variety of malignant and non-malignant disorders. With improved outcomes after HSCT, increasing attention has been drawn to late complications in long-term survivors. The development of secondary malignancies is recognized as one of the most serious complications. We have evaluated data from 426 patients (272 males, 154 females) who underwent allogeneic transplantation at a median age of 7.9 years from 1989 till 2017 and were alive more than one year after transplantation for the occurrence of secondary solid tumors. We have documented the occurrence of secondary solid tumors in 20 patients (4.7%). The median duration of the development of secondary solid cancer from HSCT was 11.7 (range, 5.4-21.5 years). 18 out of 20 patients (90%) had total body irradiation (TBI) 12-14.4 Gy as a part of a conditioning regimen. All but two had transplantation for malignant disease. All patients underwent surgery and/or chemo-radiotherapy. Eighteen are alive, and two died due to the progression of their secondary malignancy. The most frequent solid cancer was thyroid carcinoma (n=9). Cumulative incidence of secondary solid cancer in all groups was 15.2±3.9%, in a group using TBI based regimen 34.7±8.9%, in non-TBI (only chemo) group was 1.5±1.1%. Overall, the cumulative incidence is statistically significantly different between the TBI based and non-TBI (chemo only) group. The incidence and number of complications following allogeneic HSCT in childhood are increasing in time. The early diagnosis of secondary malignancies is one of the key tasks of long-life multidisciplinary post-transplant care.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for a variety of malignant and non-malignant disorders. The prevalence of HSCT survivors continues to increase. Gonadal insufficiency and infertility are amongst the most frequent late complications. Methods: Data on successful pregnancies following HSCT in childhood were analyzed in 180 patients older 18 years (all transplanted at our center). Median age at the time of HSCT was 15.5 (8.0 - 19.9) years. Results: 25 of 180 (14%) subjects (males=14, females=11) became parents. Of them non-malignant severe aplastic anemia (SAA) had 12 (48%) subjects and another 13 had malignant diagnosis: acute lymphoblastic (ALL; n=6), acute myeloid (AML; n=1) and chronic myeloid (CML; n=3) leukemia; remaining 3 patients had myelodysplastic syndrome (MDS). Forty children were born to the overall group, 34 out of 40 (85%) in term, all were healthy. First pregnancy (both spontaneous or after assisted reproduction) was documented 10.4 (2.5 - 24) years after HSCT in patient´s median age 26.3 (18.3 - 41.2) years. Spontaneous gravidity was detected in 16 subjects (males=9, spermiogram evaluated in 8 of them; females= 7, spontaneous regular menstrual cycle had 5 of them). Majority of subjects had HSCT due to SAA (75%; 7 males and 5 females) with cyclophosphamide regimen only. In 2 males full myeloablative Busulphan based conditioning was used (MDS, AML), and 2 females (MDS and CML, both with hormonal replacement therapy and possibility of some residual oocyte reserve) become pregnant after previously repeated unsuccessful assisted reproduction techniques (ART) with ovarian hyperstimulation (even one after total body irradiation 14.4 Gy based regimen). In remaining 9 subjects successful pregnancy was achieved after ART (donor sperm=1, cryopreserved sperm =2, TESE=2, donor oocytes=4). Conclusions: Gonadotoxicity after HSCT and infertility are the well-known posttransplant complications negatively affecting the quality of life. Fertility issues must be routinely discussed at peritransplant care. In the field of reproductive medicine impressive advances have been achieved to offer the best option for fertility preservation and pregnancy outcome. Better knowledge of pregnancy rate especially in pediatric population following HSCT will require more data for analysis in international cooperation. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.