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Background Serine/threonine kinase 4 (STK4) deficiency is a combined immunodeficiency (CID) characterized by early onset recurrent bacterial, viral, and fungal infections. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for CID; however, little is known about the necessity and benefits of HSCT in patients with STK4 deficiency. Methods We report two siblings with STK4 deficiency transplanted from two unrelated donors with the same conditioning regimen. Results In the conditioning regimen, rituximab was given on Day -11 (375 mg/m(2)), and sirolimus was added on the same day. Busulfan was administered at a myeloablative dose (3.2 mg/kg; Days -7 to -4) with 150 mg/m(2) of fludarabine (Days -7 to -3). They were transplanted with peripheral blood stem cells, and graft-versus-host disease (GVHD) prophylaxis was administered with 10 mg/m(2) methotrexate on Days 1, 3, and 6. In addition, mycophenolate mofetil (MMF) was started on Day 1 with ongoing use of sirolimus. We did not encounter veno-occlusive disease (VOD), high-grade acute GVHD, or significant organ toxicity in either patient. Both patients were well at the end of the first year after HSCT with complete donor chimerism. Conclusions Serine/threonine kinase 4 deficiency is a disease with high mortality post-HSCT; therefore, the conditioning regimen and GVHD prophylaxis strategies are important considerations in these patients. In our opinion, the conditioning regimen, which includes rituximab and busulfan and fludarabine (BU-FLU), GVHD prophylaxis with sirolimus and MMF, and short-term methotrexate, offers favorable outcomes and is well tolerated in our STK4-deficient patients. WOS:000884588000001 Q4

Diamond Blackfan anemia (DBA) is a rare congenital syndrome presenting primarily as pure red cell aplasia with constitutional abnormalities and cancer predisposition. Established treatment options are corticosteroids, regular erythrocyte transfusions with iron chelation therapy, and hematopoietic stem cell transplantation (HSCT). To date, HSCT is the only definitive curative treatment for the hematological phenotype of DBA, but there is little experience with its use. Given the rarity of the disease and its unique features, an expert panel agreed to draw up a set of recommendations on the use of HSCT in DBA to guide clinical decision-making and practice. The recommendations address indications, pretransplant patient evaluation, donor selection, stem cell sources, conditioning regimens, prophylaxis of rejection and graft versus host disease, and post-transplant follow-up.

Background Total body irradiation (TBI) is the cornerstone of conditioning regimens in pediatric hematopoietic stem cell transplantation for acute lymphoblastic leukemia. As the late effects and survival comparison between TBI and chemotherapy were well analyzed before, in this study, we aim to focus on the first 100 days and early complications of transplantation. Methods This retrospective study involves 72 pediatric patients (0 to 18 y) underwent first hematopoietic stem cell transplantation for acute lymphoblastic leukemia between October 2015 and May 2019. Patients are divided into 2 groups regarding conditioning regimens. Conditionings includes either TBI 1200 cGy/6 fractions/3 days and etoposide phosphate or busulfan, fludarabine, and thiotepa. Busulfan was administered IV and according to body weight. Results The incidences of acute graft versus host disease grade 2 to 4, veno-occlusive disease, capillary leakage syndrome, thrombotic microangiopathy, blood stream infection, hemorrhagic cystitis and posterior reversible encephalopathy syndrome before day 100 were similar for both conditioning regimens; however, patients received TBI-based conditioning had significantly longer neutrophil engraftment time (17.5 vs. 13 d, P=0.001) and tended to have more engraftment syndrome (ES) (45.5% for TBI vs. 24.0% for chemotherapy, P=0.069). Multivariate analysis showed that TBI-based conditioning was associated with a longer neutrophil engraftment time (hazard ratio [HR]=1.20, P=0.006), more cytomegalovirus (CMV) reactivation (HR=3.65, P=0.038) and more ES (HR=3.18, P=0.078). Conclusions Our findings support chemotherapy-based regimens with early neutrophil engraftment, less ES and CMV reactivation compared with TBI. Although there is no impact on survival rates, increased incidence of ES and CMV reactivation should be considered in TBI-based regimens.

Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.

Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for bone marrow failure or hematopoietic malignant diseases for Fanconi anemia (FA) patients. Although results have improved over the last decades, reaching more than 90% survival when a human leukocyte antigen (HLA)-identical donor is available, alternative HCT donors are still less reported. We compared HCT outcomes using HLA-mismatched unrelated donors (MMUD; n = 123) or haplo-identical donors (HDs), either using only in vivo T cell depletion (n = 33) or T cells depleted in vivo with some type of graft manipulation ex vivo (n = 59) performed for FA between 2000 and 2018. Overall survival (OS) by 24 months was 62% (53–71%) for MMUD, versus 80% (66–95%) for HDs with only in vivo T cell depletion and 60% (47–73%) for HDs with in vivo and ex vivo T cell depletion (p =.22). Event-free survival (EFS) was better for HD-transplanted FA patients with only in vivo T cell depletion 86% (73–99%) than for those transplanted from a MMUD 58% (48–68%) or those with graft manipulation 56% (42–69%) (p =.046). Grade II-IV acute graft-versus-host disease (GVHD) was 41% (MMUD) versus 40% (HDs with no graft manipulation) versus 17% (HDs with T cell depleted graft), (p =.005). No differences were found for the other transplant related outcomes. These data suggest that HDs might be considered as an alternative option for FA patients with better EFS using unmanipulated grafts. © 2021 Wiley Periodicals LLC., The authors are particularly thankful to all centers from the Severe Aplastic Anemia Working Party and the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation, who kindly agreed to participate in this study (see Appendix S1). We would also like to thank Anne E. Lippinkhof, Study Coordinator, Severe Aplastic Anemia Working Party for her invaluable help.

Although advancements have been made in monitoring and preventing viral infections in HSCT patients, CMV reactivation still remains a critical post-transplant complication. Adoptive cell therapy is an alternative to pharmacotherapy of CMV infection in refractory patients. We retrospectively reviewed CMV infection cases after allogeneic HSCT who received U-DLI as treatment. In total, five pediatric patients between the ages of 0.5-16 years that received U-DLI for a post-HSCT CMV infection were evaluated. The dose of CD3+ lymphocytes administered in DLI was 5 × 104 /kg, except in one patient transplanted from his sibling. One patient, who was transplanted from an unrelated donor, received U-DLI from his haploidentical mother. CMV titers dramatically reduced after U-DLI. If the availability of CMV-specific CTL is an issue, we propose that one should consider using the U-DLI therapy with low cell dose from a seropositive donor. In case the stem cell donor is seronegative and a seropositive donor is unavailable, using the U-DLI therapy from seropositive, haploidentical donors is a promising way of treatment. More studies need to be conducted to further confirm the safety and efficacy of this treatment procedure. WOS:000579223100001 33073505 Q4

Allogeneic HSCT represents the only potentially curative treatment for very high risk (VHR) ALL. Two consecutive international prospective studies, ALL-SCT-(I)BFM 2003 and 2007 were conducted in 1150 pediatric patients. 569 presented with VHR disease leading to any kind of HSCT. All patients >2 year old were transplanted after TBI-based MAC. The median follow-up was 5 years. 463 patients were transplanted from matched donor (MD) and 106 from mismatched donor (MMD). 214 were in CR1. Stem cell source was unmanipulated BM for 330 patients, unmanipulated PBSC for 135, ex vivo T-cell depleted PBSC for 62 and cord-blood for 26. There were more advanced disease, more ex vivo T-cell depletion, and more chemotherapy based conditioning regimen for patients transplanted from MMD as compared to those transplanted from MSD or MD. Median follow up (reversed Kaplan Meier estimator) was 4.99 years, median follow up of survivals was 4.88, range (0.01–11.72) years. The 4-year CI of extensive cGvHD was 13 ± 2% and 17 ± 4% (p = NS) for the patients transplanted from MD and MMD, respectively. 4-year EFS was statistically better for patients transplanted from MD (60 ± 2% vs. 42 ± 5%, p p

We examined outcomes of 51 pediatric patients with relapsed acute leukemia (AL) who underwent a second allogeneic hematopoietic stem cell transplantation (alloHSCT). After a median follow-up of 941 days (range, 69-2842 days), leukemia-free survival (LFS) and overall survival (OS) at 3 years were 26.6% and 25.6%, respectively. The nonrelapse mortality rate (NMR) and cumulative incidence of relapse (CIR) were 36.4% and 42.4%, respectively. The Cox regression analysis demonstrated that the risk factors at second transplantation for predicting limited LFS were active disease (hazard ratio (HR) = 5.1), reduced intensity conditioning (RIC) (HR = 5.0), matched unrelated donor (MUD) (HR = 3.4) and performance score

Uygun, Vedat ; Karasu, Gulsun Tezcan (isu author) Deficiency of the CD40L, expressed on the surface of T lymphocytes, is caused by mutations in the glycoproteinCD40L (CD154)gene. Resulting defective humoral and cellular responses cause a clinical presentation that includes recurrent sinopulmonary bacterial infections, opportunistic infections, sclerosing cholangitis, neutropenia, and autoimmune manifestations. HSCT represents the only curative treatment modality. However, the therapeutic decision to use HSCT proves challenging in many cases, mainly due to the lack of a phenotype-genotype correlation. We retrospectively reviewed patients with CD40L deficiency who were transplanted in Antalya and Goztepe MedicalPark Pediatric HSCT units from 2014 to 2019 and followed by Akdeniz University School of Medicine Department of Pediatric Immunology. The records of eight male cases, including one set of twins, were evaluated retrospectively. As two transplants each were performed on the twins, a total of ten transplants were evaluated. Conditioning regimens were predominantly based on myeloablative protocols, except for the twins, who received a non-myeloablative regimen for their first transplantation. Median neutrophil and platelet engraftment days were 13 (range 10-19) and 14 (range 10-42) days, respectively. In seven of ten transplants, a CMV reactivation was developed without morbidity. None of the patients developed GVHD, except for one mild case of acute GVHD. All patients survived, and the median follow-up was 852 days. Our data show that HSCT for patients with CD40 ligand deficiency is a potentially effective treatment for long-term disease control. WOS:000541941200001 32573870 Q4

Background: Post-transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data on risk factors, treatment options, and outcomes are limited. Procedure: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo-HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo-HSCT. Results: The median interval from transplantation to relapse was 180 days, and the median follow-up from relapse to the last follow-up was 1844 days. The 3-year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo-HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P = .011) and relapse earlier than 365 days post-transplantation (HR: 2.101, P < .001 for 0-180 days; HR: 1.522, P = .041 for 181-365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS. Conclusion: A salvage approach with curative intent may be considered for patients with post-transplant relapse, even if they relapse in the first year post-transplantation. For sustainable remission, a second allo-HSCT may be recommended for patients who achieve complete remission after reinduction treatment. WOS:000598672000001 33320995 Q4

Mutations in interleukin-10 and its receptors cause infantile inflammatory bowel disease (IBD), a hyperinflammatory disorder characterized by severe, treatment-refractory colitis, multiple abscesses, and enterocutaneous fistulas. Patients with infantile IBD often require several surgical interventions, including complete colectomy, and hematopoietic stem cell transplantation is currently the only known medical therapy. Traditionally, operative management has been preferred before stem cell transplantation because of the latter's increased susceptibility to procedural complications; however, surgical intervention could be delayed, and possibly reconsidered, because our 2 patients with infantile IBD demonstrated a rapid response to treatment via engraftment.

Post-Cy administration for GVHD prophylaxis in unmanipulated haploidentical HSCT has resulted in improved outcomes in recent years. Studies in children are lacking and accordingly we present the outcomes of 62 haploidentical transplantation for high-risk children.We retrospectively assessed 62 transplants in 60 patients who underwent haploidentical-related HSCT with unmanipulated stem cells and for whom Post-Cy was used for GVHD prophylaxis.Myeloid reconstitution was achieved on day + 30 for 57 of the 62 patients. The median follow-up of the surviving 39 patients (63%) was 26 months, with a range of 6-57 months. The OS and EFS at 2 years were 64.6% (52.0%-77.2%, 95% CI) and 58.9% (46.1%-71.7%, 95% CI), respectively. The only factor in our multivariate analysis that contributed to an inferior EFS was a poor remission status prior to HSCT (HR, 8.30; 1.08-63.56; P = 0.041, 95% CI).The results of T-cell replete haploidentical transplantation with Post-Cy GVHD prophylaxis in high-risk pediatric patients are promising. However, further research is needed to determine the factors that have affect HLA compatibility for predicting the success of haploidentical transplantations.

EgeUn###, Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P =.011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P =.012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P =.014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P =.007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P =.063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%. The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Elhan, Atilla Halil/0000-0003-3324-248X; Ikinciogullari, Aydan/0000-0003-1145-0843; Dogu, Figen/0000-0002-7869-4941; ates, can/0000-0003-2286-4398 WOS: 000468974100018 PubMed: 30924026 Severe combined immunodeficiency (SCID) is the most serious PID, characterized by T cell lymphopenia and lack of antigen-specific T cell and B cell immune responses, inevitably leading to death within the first year of life if hematopoietic stem cell transplantation (HSCT) is not performed. Purpose and Methods Since SCID is a common type of PID with an estimated incidence of 1/10.000 in Turkey, a retrospective analysis of HSCT characteristics, survival, immune recovery, and the major clinical features of SCID prior to HSCT is the aim of this multi-transplant center-based analysis. Results A total of 234 SCID patients transplanted between the years 1994 and 2014 were included in the study. Median age at diagnosis was 5 months, at transplantation, 7 months, B- phenotype and RAGs were the most common defects among others. Immune phenotype did not seem to have an effect on survival rate (p > 0.05), Immunoglobulin (Ig) requirement following HSCT did not differ between B+ and B- phenotypes (p > 0.05). Overall survival rate was 65.7% over a period of 20 years. It increased from 54% (1994-2004) to 69% (p = 0.052) during the last 10 years (2005-2014). Ten-year survival after HSCT has improved over time although the difference was not significant. Infection at the time of transplantation (p = 0.006), mismatched related donor (MMRD) (haploidentical parents), and matched unrelated donor (MUD) donor transplants p < 0.001 were the most important factors, significantly affecting the outcome. Conclusions This is the first multicenter study with the largest data obtained from transplanted SCID patients in Turkey. Early diagnosis with newborn screening (NBS) together with emerging referrals, treatment by transplantation centers, and specialized teams are mandatory in countries with high parental consanguinity such as Turkey.

Allogeneic hematopoietic stem cell transplantation (HSCT) is beneficial for pediatric patients with relapsed or (very) high-risk acute lymphoblastic leukemia (ALL) in remission. A total of 1115 consecutive patients were included in the ALL SCT 2003 BFM study and the ALL SCT 2007 I-BFM study and were stratified according to relapse risk (standard versus high versus very high risk of relapse) and donor type (matched sibling versus matched donor versus mismatched donor). A total of 148 patients (60% boys; median age, 8.7 years; B cell precursor ALL, 75%) were transplanted from mismatched donors, which was defined as either less than 9/10 HLA-compatible donors or less than 5/6 unrelated cord blood after myeloablative conditioning regimen (total body irradiation based, 67%) for high relapse risk (HRR; n = 42) or very HRR (VHRR) disease (n = 106). The stem cell source was either bone marrow (n = 31), unmanipulated peripheral stem cells (n = 28), T cell ex vivo depleted peripheral stem cells (n = 59), or cord blood (n = 25). The median follow-up was 5.1 years. The 4-year rates of overall survival (OS) and event-free survival were 56% ± 4% and 52% ± 4%, respectively, for the entire cohort. Patients transplanted from mismatched donors for HRR disease obtained remarkable 4-year OS and event-free survival values of 82% ± 6% and 80% ± 6%, respectively, whereas VHRR patients obtained values of 45% ± 5% and 42% ± 5% (P .001), respectively. The cumulative incidence of relapse was 29% ± 4% and that of nonrelapse mortality 19% ± 3%. The cumulative incidence of limited and extensive chronic graft-versus-host disease was 13% ± 3% and 15% ± 4%, respectively, among the 120 patients living beyond day 100. Multivariate analysis showed that OS was lower for transplanted VHRR patients (P = .002; hazard ratio [HR], 3.62; 95% confidence interval [CI], 1.60 to 8.20) and for patients beyond second complete remission (CR2) versus first complete remission (P .001; HR, 3.68; 95% CI, 1.79 to 7.56); relapse occurred more frequently in patients with VHRR disease (P = .026; HR, 3.30; 95% CI, 1.16 to 9.60) and for those beyond CR2 (P = .005; HR, 4.16; 95% CI, 1.52 to 10.59). Nonrelapse mortality was not significantly higher for cytomegalovirus-positive recipients receiving cytomegalovirus-negative grafts (P = .12; HR, 1.96; 95% CI, .84 to 4.58). HSCT with a mismatched donor is feasible in pediatric ALL patients but leads to inferior results compared with HSCT with better matched donors, at least for patients transplanted for VHRR disease. The results are strongly affected by disease status. The main cause of treatment failure is still relapse, highlighting the urgent need for interventional strategies after HSCT for patients with residual leukemia before and/or after transplantation.

KILIC, SUAR CAKI/0000-0001-7489-2054; Emir, Levent/0000-0003-2424-3763; Hazar, Volkan/0000-0002-1407-2334 WOS: 000412118800010 PubMed: 28571522 We examined outcomes of 62 pediatric patients with relapsed or refractory non-Hodgkin lymphoma (rr-NHL) who underwent hematopoietic stem cell transplantation (HSCT). The overall survival (OS) and event-free survival (EFS) rates were 65% and 48%, respectively. Survival rates for patients with chemosensitive disease at the time of HSCT were significantly higher than those of patients with chemosensitive disease (69% vs. 37%, p = .019 for OS; 54% vs. 12%, p

The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate > 80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.

Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant diseases. Decrease in short-term complications has substantially contributed to increased survival. Therefore long-term sequelae are reaching the focus of patient care. One of the most important risks of stem cell transplant survivors is infertility. As well as in the field of allo-HSCT also the field of reproductive medicine has achieved substantial advances to offer potential options for fertility preservation in both boys and girls. Access to these procedures as well as their financing differs significantly throughout Europe. As all European children and adolescents should have the same possibility, the Paediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation organised an expert meeting in September 2015. This manuscript describes the recommendations for the diagnosis and pre-emptive procedures that should be offered to all children and adolescents in Europe who have to undergo an allo-HSCT.

INTRODUCTION Diamond-Blackfan Anemia (DBA) is a congenital pure red cell aplasia, secondary to ribosomal protein genetic defects that usually presents within the first year of age and can be associated with congenital abnormalities and increased risk of cancer. Some patients are successfully treated with steroids but most of them remain transfusion-dependent. Stem Cell Transplantation (SCT) represents the only curative option for this disease, however data from literature is scarce and limited to a very small number of cases. In this retrospective study we describe the outcome of SCT in patients with DBA reported in the EBMT data base. PATIENTS AND METHODS The study was conducted on behalf of Severe Aplastic Anemia Working Party of the EBMT and was based on data of patients affected with DBA who underwent SCT and registered in the EBMT Data Base. Clinical information of the disease and details on transplant procedures and follow-up were collected by a specific form distributed to Centres participating in the study. RESULTS Between 1985-2016, 106 patients (60 males-46 females) aged 6.8 yo (range 1-32) underwent SCT from matched sibling donor (58, 57%), unrelated donor (37, 36%) or from other donors (7, 7%) using bone marrow (73, 69%), peripheral blood (21, 20%) or cord blood (12, 11%) as cell source. 91 patients (86%) received a myeloblative regimen which included Busulfan in 66 cases. 86% (80-93%) of patients engrafted by day 28. Median days to neutrophils and platelets engraftment were 18 and 36, respectively. EFS and OS at 36 months were 81% (74-89%) and 84% (77-91%), respectively. OS was significantly higher (p=0.01) in patients CONCLUSION To the best of our knowledge, this is the largest reported cohort of patients transplanted for DBA and having a long follow-up. The very good OS of patients undergoing transplant from both sibling and unrelated donors and the rather low rate of cGvHD confirms that this procedure can be considered an alternative option for transfusion-dependent patients Disclosures Bader: Riemser, Neovii: Research Funding; Medac: Patents & Royalties, Research Funding; Amgen (Brasil), Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy. Risitano:Alexion: Honoraria, Research Funding, Speakers Bureau; Achillion: Research Funding; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biocryst: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Research Funding, Speakers Bureau; Amyndas: Consultancy; Samsung: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amyndas: Consultancy; Biocryst: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ra Pharma: Research Funding; Ra Pharma: Research Funding; Alnylam: Research Funding; Alnylam: Research Funding; Achillion: Research Funding. Peffault de Latour:Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding.

Extracorporeal photopheresis (ECP) has been used widely in the treatment of steroid-refractory chronic graft versus host disease (cGVHD). Several reports have applied an 'early treatment' approach due to the better response rates compared with late treatment. However, herein, we report a hematopoetic stem cell transplantation performed in a thalassemia major patient presenting with severe cGVHD who applied to our center for ECP treatment nearly 12 years after the onset of cGVHD.

CNL is a rare myeloproliferative disorder frequently seen in older adults. A significant proportion of patients show progression to AML. Here, we report the case of a patient with FA who was monitored for leukopenia but who developed leukocytosis during the follow-up and was diagnosed with CNL probably after an acquired CSF3R mutation. Because the patient had FA, which could accelerate the progression to AML, an HSCT was performed, which resulted in cure. This patient (aged 12 years) is one of the youngest patients reported to develop CNL as well as the first FA patient with a diagnosis of CNL.

This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty-nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU+etoposide+ara-C+melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow-up period of 39months, 46 patients were alive. At fiveyr, the probabilities of OS, EFS, the relapse rate, and the non-relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at fiveyr was 72.3% and 19%, respectively (p, This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty-nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU + etoposide + ara-C + melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow-up period of 39 months, 46 patients were alive. At five yr, the probabilities of OS, EFS, the relapse rate, and the non-relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at five yr was 72.3% and 19%, respectively (p < 0.001). Multivariate analysis showed that chemoresistant disease at the time of transplantation was the only factor predicting limited both OS (hazard ratio = 4.073) and EFS (hazard ratio = 4.599). AutoHSCT plays an important role for the treatment of rrHL in children and adolescents, and survival rates are better for patients with chemosensitive disease at the time of transplantation.

Isolated extramedullary relapse (EMR) after hematopoietic stem cell transplantation (HSCT) is a highly fatal condition that creates uncertainty regarding treatment options. Although certain approaches such as repeat HSCT and donor lymphocyte infusion are recommended, we report a patient with acute lymphoblastic leukemia who had three isolated EMRs after HSCT at different locations and at different times that were responsive to local and systemic therapies, without the need for a second transplantation.

PubMedID: 28664550 DIDS is a unique form of combined immune deficiency characterized by an unusual susceptibility to cutaneous viral infections, severe allergies with eosinophilia and elevated immunoglobulin E titers, autoimmunity, and cancer. HSCT is considered the standard of care for this deadly disease. We have retrospectively analyzed the outcome of allogeneic HSCT from unrelated donors in patients with DIDS. Data from four patients, with five transplants, are presented. All patients received transplants from unrelated donors' BM, except for one patient who received a cord blood transplant. The conditioning regimens were based on myeloablative protocols for BM derived transplants; a NM regimen was pursued for the patient who received a cord blood transplant, which resulted in graft rejection. Although recurrent pneumonia and skin infections resolved immediately after transplantation, all patients subsequently developed human herpesvirus infection, including cutaneous herpetic lesions, cytomegalovirus reactivation, and zona zoster, which could be attributed to the use of ATG. Despite the presence of serious morbidities prior to transplantation, all patients recovered successfully. DIDS can be successfully treated with allogeneic HSCT from unrelated donors following a myeloablative conditioning regimen, with a reasonable safety profile. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

IHA is characterized by a sudden increase in plasma ammonia levels in the absence of any identifiable causes, which mostly results in intractable coma and high mortality. It has been reported in some patients after receiving intensive chemotherapy for hematological malignancy or HSCT. We describe a case of a patient with FA that developed acute idiopathic hyperammonemia after the preparative regimen for HSCT.

PNP deficiency is a rare combined immunodeficiency with autosomal recessive mode of inheritance. The immunodeficiency is progressive with normal immune functions at birth, but then, T-cell deficiency with variable B-cell functions usually presents by the age of two yr. The only curative treatment for PNP deficiency is hematopoietic stem cell transplantation. Here, we present a 13-yr-old girl with late-onset PNP deficiency. Despite many complications of infections, she was successfully transplanted with a reduced intensity-conditioning regimen from an HLA-identical unrelated donor.