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Sinusoidal obstruction syndrome/venoocclusive disease is a significant complication of hematopoietic stem cell transplantation. Due to high mortality rates, new treatment strategies have been investigated. Here, we have presented outcomes of therapeutic plasma exchange performed on patients with sinusoidal obstruction syndrome/veno-occlusive disease.Our study included 70 pediatric patients diagnosed with sinusoidal obstruction syndrome/veno-occlusive disease. Therapeutic plasma exchange procedures in patients were evaluated retrospectively.There were 9 mild (12.9%), 9 moderate (12.9%), 21 severe (30%), and 31 very severe (44.2%) cases of sinusoidal obstruction syndrome/venoocclusive disease. Therapeutic plasma exchange was performed in 31 of the 70 study patients (59.6%). Moreover, 10/21 patients with severe (47.6%) and 21/31 patients with very severe (67.7%) disease underwent plasma exchange. Mean time from diagnosis of sinusoidal obstruction syndrome/venoocclusive disease to therapeutic plasma exchange initiation was 2.3 days. The 31 patients who received therapeutic plasma exchange had a total of 146 sessions. Overall survival rates at 100 days were 87.1% and 92.3% for patients who did and did not undergo therapeutic plasma exchange, respectively. When patients with mild and moderate disease who were not expected to undergo plasma exchange were excluded (n = 52), 100-day overall survival rates were 87.1% and 90.5% for those who did and did not undergo plasma exchange, respectively. When we compared severe versus very severe groups, no significant difference was found.Plasmapheresis had no positive effect on survival. However, overall survival in all groups was higher than that in the literature, despite the high number of patients with severe and very severe disease. Interpretation of the results is limited by the retrospective nature of the study. Thus, prospective, randomized controlled trials with larger numbers of patients are necessary to investigate the role of therapeutic plasma exchange in patients with sinusoidal obstruction syndrome/veno-occlusive disease.

Background: Data on the outcome and risk factors of pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. Objectives: We aimed to describe risk factors for a severe course and mortality. Method: In this nationwide study, data were collected retrospectively from 28 transplant centers. Results: One hundred ninety-six children [(63.8% male; median age 8.75 (IQR, 4.86-14.30)] who received allogeneic (n: 184, 93.9%) or autologous (n: 12, 6.1%) HSCT were included. The median time from HSCT to SARS-CoV-2 infection was 207.5 days (IQR, 110.2-207.5). The most common clinical manifestation was fever (58.2%), followed by cough (33.7%); 43 cases (21.9%) were asymptomatic. Lower respiratory tract disease (LRTD) and multisystem inflammatory syndrome in children (MIS-C) developed in 58 (29.6%) and 8 (4.1%) patients, respectively. Twenty-six patients (13.3%) required ICU admission. Nine patients died at a median of 17 days (min-max 1-33) after COVID-19 diagnosis, 6 of whom died due to the disease, with a COVID-19 lethality rate of 3.1%. The 6-week overall survival was 95.4% (95% CI 92.5-98.3). Multivariate analysis found that HSCT with a mismatched donor (OR, 8.98, p: 0.039) and LRTD (OR, 61.55, p: 0.001) were independent risk factors for ICU admission; MIS-C (OR, 9.55, p: 0.044) and lymphopenia (OR, 4.01, p: 0.030) at diagnosis were risk factors for mortality. Conclusion: Overall mortality was lower in children than in adult counterparts, and HSCT with a mismatched donor, lymphopenia, LRTD, MIS-C and ICU admission were important risk factors for adverse outcomes.

Introduction In highly sensitized patients who have panel reactive antibodies (PRAs) before hematopoietic stem cell transplantation, primary graft failure risk may increase. In this study, we aimed to determine the association of PRA with engraftment, and graft versus host disease (GVHD) in pediatric patients. Materials and methods Forty-three PRA-positive and 42 PRA-negative patients were taken into study. Both groups were compared in terms of graft failure, acute GVHD, viral infection and survival rates. PRA-positive group was also divided into 2 according to treatment modality (steroid-only group/combination therapy) and compared for the same parameters. Results There was no difference in PRA-positive and negative patients in terms of graft failure, acute GVHD and viral infections. Analysis of the PRA-positive group in itself showed that there was also no difference in terms of graft failure and viral infection frequency. The only difference is that acute grade 3 to 4 GVHD was higher in the steroid-only group. The 100-day overall survival was 90.2% and 90.4% for the PRA-positive and negative groups, respectively. Conclusions Different treatment strategies like plasmapheresis, steroid, rituximab, or combination therapies can be used for the desensitization of PRA-positive patients before hematopoietic stem cell transplantation. Patient-specific treatment modality for sensitized patients before transplant can increase the success rate.

Purpose Patients with heterozygous gain-of-function (GOF) mutations in STAT1 frequently exhibit chronic mucocutaneous candidiasis (CMC), immunodeficiency and autoimmune manifestations. Several treatment options including targeted therapies and hematopoietic stem cell transplantation (HSCT) are available for STAT1 GOF patients but modalities and outcomes are not well established. Herein, we aimed to unravel the effect of ruxolitinib as a bridge therapy in a patient with sporadic STAT1 T385M mutation to manage infections and other disease manifestations. Methods Peripheral blood mononuclear cells were isolated from the patient prior to, during ruxolitinib treatment and 6 months after HSCT. IFN-beta-induced STAT1 phosphorylation/dephosphorylation levels and PMA/ionomycin-stimulated intracellular IL-17A/IFN-gamma production in CD4(+) T cells were evaluated. Differentially expressed genes between healthy controls and the patient prior to, during ruxolitinib treatment and post-transplantation were investigated using Nanostring nCounter Profiling Panel. Results Ruxolitinib provided favorable responses by controlling candidiasis and autoimmune hemolytic anemia in the patient. Dysregulation in STAT1 phosphorylation kinetics improved with ruxolitinib treatment and was completely normalized after transplantation. T(H)17 deficiency persisted after ruxolitinib treatment, but normalized following HSCT. Consistent with the impairment in JAK/STAT signaling, multiple immune related pathways were found to be dysregulated in the patient. At baseline, genes related to type I IFN-related pathways, antigen processing, T-cell and B-cell functions were upregulated, while NK-cell function and cytotoxicity related genes were downregulated. Dysregulated gene expression was partially improved with ruxolitinib treatment and normalized after transplantation. Conclusion Our findings suggest that improved disease management and immune dysregulatory profile can be achieved with ruxolitinib treatment before transplantation and this would be beneficial to reduce the risk of adverse outcome of HSCT.

Mesenchymal stem cells (MSCs) have been used systemically or locally in many chronic and nonhealing skin lesions in recent years. In this study, umbilical cord-derived MSCs (UC-MSCs)-seeded fibrin matrix was used as a wound dressing in pediatric patients with stage 4 acute graft-versus-host disease (aGVHD)-induced desquamated skin lesions. This is the first study in which the UC-MSCs-seeded fibrin matrix was used as a wound dressing in aGVHD. A total of 14 times the MSCs-seeded fibrin matrix were applied to 9 patients as a wound dressing. On the seventh day, epithelialization and clinical response were evaluated. According to the size of the skin defect min: 1, max: 6 pieces were applied at a time. After 48 to 72 hours, it was observed that all of the MSCs-seeded fibrin matrixes adhered to the skin and the crustation started in 6 (43%) applications, whereas liquefaction was detected under all of them in 7 (50%) applications. Complete response was obtained in 6 applications (43%), partial response in 1 (7%), and no response in 7 applications (50%). This study showed that the MSCs-seeded fibrin matrix can be used effectively and safely in the matrix in the local treatment of aGVHD-induced skin wounds in pediatric patients.

This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA).Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h.Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p0.05).Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.Geriye dönük çok merkezli bir çalışma düzenleyerek, çocuk hematoloji uzmanlarının sistemik rekombinant doku plazminojen aktivatörü (rtPA) kullanımı ile ilgili deneyimlerinin ortaya konması amaçlandı.Türkiye’deki 13 pediatrik hematoloji merkezinden geriye dönük veriler toplandı. rtPA tedavisinin dozu ve süresi, eşzamanlı antikoagülan tedavi, tam pıhtı erimesi (TPE), kısmi pıhtı erimesi (KPE) ve kanama komplikasyonları değerlendirildi. Düşük doz (DD) rtPA tedavisi 0,01-0,06 mg/kg/saat ve yüksek doz (YD) 0,1-0,5 mg/kg/saat olarak tanımlandı.2005-2019 yılları arasında ortanca yaşı 5 yıl (1 gün-17,75 yıl) olan 54 hastanın 55 trombotik epizodu değerlendirildi. Hastaların tanıları; intrakardiyak tromboz (n=16), derin ven trombozu (DVT) (n=15), inme dışı arteriyel tromboz (n=14), pulmoner tromboemboli (PE) (n=6) ve inme (n=4) idi. Trombüs saptanmasından rtPA başlangıcına kadar geçen süre medyan 12 saat (2 sa-504 sa) idi ve inme, inme olmayan arteriyel tromboz ve intrakardiyak tromboza kıyasla DVT ve PE için anlamlı olarak daha uzundu (p=0,024). Atakların %63,6’sında rtPA tedavisinden önce heparin başlandı. Atakların 22’sine DD ve 33’üne YD rtPA uygulandı. DD ve YD rtPA ataklarının sırasıyla %90’ında ve %36’sında eş zamanlı antikoagülasyon kullanıldı (p=0,0001). DD ve YD rtPA infüzyonlarının medyan toplam süresi sırasıyla 30 sa (2 sa-120 sa) ve 18 sa (2 sa-120 sa) idi (p=0,044). Ölümcül olmayan majör ve minör kanama oranları DD için sırasıyla %12,5, %16,7 ve YD rtPA için %3,2, %25,8 idi. rtPA infüzyonlarının sonunda, atakların sırasıyla %32,7’sinde TPE ve %49’unda KPE elde edildi. Tromboliz için en başarılı bölge intrakardiyak trombozdu. YD’ye karşı DD rtPA uygulaması, TPE/KPE veya kanama ile korele değildi (p0,05).Yüksek riskli trombozlu çocuklarda sistemik trombolitik tedavi, deneyimli hematologlar tarafından rekanalizasyon ve kanamanın yakın takibi altında doğru endikasyon ve doğru zamanda kullanıldığında etkin bir şekilde hayat ve organ kurtarabilir.

Background Haploidentical HSCT is a good option for children with PIDs lacking an HLA-matched donor. Co-transplantation of MSCs during haploidentical HSCT in patients with PIDs may enhance engraftment, decrease the risk of GVHD, and ensure stable donor chimerism. Methods Twenty-seven pediatric patients (median age, 1.4 years; range, .3-10.9) with PIDs undergoing thirty haploidentical HSCT with TCR αβ depletion and co-transplantation of MSCs were enrolled to study. Most patients (73.3%) received myeloablative conditioning consisting of treosulfan or busulfan, fludarabine, and thiotepa. The median duration of follow-up was 14.3 months (range, 1-69 months). Results Acute GVHD occurred in 7 patients (grade I-II n = 5, grade III-IV n = 2). Chronic GVHD was observed in only one patient. Twenty-one patients (70.2%) had 100% donor chimerism in all cell lines including T-cell and B-cell lineages. Primary graft failure was observed in 7 patients (25.9%). The cumulative incidences of TRM were 20% at day 100, and 26.7% at one year and five years. Probabilities of OS were 80% at day 100, and 71.9% at 1 year and 5 years. Infants transplanted younger than 6 months of age had the highest 5-year survival rate (85.7%). Conclusion We conclude that use of TCR αβ depleted haploidentical transplantation with MSCs may ensure a rapid engraftment rate, low incidence of significant acute and chronic GVHD, and acceptable post-transplantation morbidity, especially in patients diagnosed with SCID and may be considered in children with PIDs. In younger patients (≤6 months), survival is comparable between HLA-matched graft and CD3+ TCRαβ depleted HLA-mismatched graft recipients.

Objectives The most important problems that limit the effectiveness of allogeneic hematopoietic stem cell transplantation in patients with severe aplastic anemia are graft failure and graft-versus-host disease. Mesenchymal stem cells can support normal hematopoiesis and prevent graft-versus-host disease. We aimed to analyze the effects of combined transplant of human umbilical cord-derived mesenchymal stem cells and matched donor allogeneic hematopoietic stem cells in children with severe aplastic anemia. Materials and methods We retrospectively examined 15 pediatric patients with severe aplastic anemia who received fludarabine-based reduced intensity conditioning regimen and intravenously infused human umbilical cord-derived mesenchymal stem cells at a dose of 1 × 106/kg recipient body weight within 12 to 18 hours before hematopoietic stem cells infusion. We evaluated the engraftment rate, the frequency and severity of graft-versus-host disease, and the overall survival rate. Results No patients had adverse events related to intravenously human umbilical cord-derived mesenchymal stem cells infusion. All patients achieved successful engraftment and sustained donor chimerism. The median time for neutrophil and platelet engraftment was 14 and 25 days, respectively. The frequency was 20% for grade III/IV acute graftversus-host disease and 15.3% for chronic graftversus-host disease. Patients were followed-up for a median of 33 months (range, 2-89 months). The 5-year overall survival rate was 80%. Conclusions Combined transplant of matched donor hematopoietic stem cells with human umbilical cord-derived mesenchymal stem cells is safe in pediatric patients with severe aplastic anemia. The achievement of engraftment in all of our patients and the acceptable frequency of acute and chronic graft-versus-host disease and survival rate are encouraging.

BACKGROUND Anti-human T-lymphocyte immunoglobulin is commonly used as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors. The studies according to optimum dose of ATLG especially in pediatric patients are limited. PATIENTS AND METHODS Outcomes of 99 pediatric patients diagnosed with nonmalignant diseases, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2), and 30 mg/kg (group 3), were analyzed retrospectively. RESULTS The incidences of acute and chronic GVHD were statistically not different between three groups (p = .20 and p = .13), but we did not observe chronic GVHD in group 3 patients. Cox regression analysis showed that ATLG dose of 10 mg/kg (p = .007) and severe acute GVHD (p = .001) were significant prognostic factors for inferior overall survival. Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention, TRM and overall survival were superior in ATLG doses ≥20 mg/kg (p = .04 and p = .037) with no difference between 20 and 30 mg/kg. CONCLUSION Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection, TRM and OS were superior in ATLG doses ≥20 mg/kg with no difference between 20 and 30 mg/kg. These observations should be supported with other multicenter prospective studies including larger patient population.

WOS:000614296900001 PMID: 33538100 Adults with cancer are reported to have a higher risk for coronavirus disease (COVID-19) infection and more severe disease and mortality than the general population.1,2 Although children seem to be at a lower risk for COVID-19 than adults,3–5 data specifically addressing children with cancer are limited

Background: Graft versus host disease is a major cause of morbidity and mortality after allogeneic HSCT from unrelated donors. ATLG is commonly used as prophylaxis for GVHD. The studies according to optimum dose of ATLG especially in pediatric patients are limited. Patients and Methods: Outcomes of 158 pediatric patients, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2) and 30 mg/kg (group 3) were analyzed retrospectively. The median duration of follow-up was 25.25 months (range, 1.1-79.5 months). Results: The incidences of acute and chronic GVHD were statistically not different between three groups (p=0.55 and p=0.45). But TRM at day 100 and OS at the end of follow-up was found significant inferior in patients received ATLG 10 mg/kg (p=0.006, p=0.004). Cox regression analysis showed that ATLG dose of 10 mg/kg (hazard ratio [HR] 0.500 [95% CI 0.301-0.829]; p=0.007), severe acute GVHD (HR 5.512 [2.027-14.993]; p=0.001), and having viral infection (HR 2.510 [1.034-6.089]; p=0.042) were significant prognostic factors for inferior OS. Conclusion: Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection; TRM and OS were superior in ATLG doses ≥20 mg/kg with no difference between 20 mg/kg and 30 mg/kg. So, it could be better to choose ATLG dose of 20 mg/kg in conditioning regimen for MUD HSCT in pediatric patients, but these observations should be supported with other multicenter prospective studies including larger patient population.

Background RhD typing has remained of primary importance, as being the leading cause of hemolytic disease of the newborn. Among Rh system’s 55 blood group antigens, RhD is the most immunogenic. We aimed with this study to determine weak D/partial D variant frequency in blood donors who were admitted to our blood center and have serologically designated blood group weak D. Materials and methods We screened blood donors who admitted between 2011 and 2017 to our blood center. Sixty-seven serologically weak D phenotyped donors have participated in the study. These donors' samples were studied further by Polymerase Chain Reaction Sequence- Specific Primers (PCR-SSP) for determining D variants. Results Weak D phenotype was detected in 228(0.12 %) out of 177,554 donors. Sixty-seven of them agreed to take part in the study. The frequency of weak D and partial D was 68.7 % (n = 46), and 22.4 % (n = 15), in order. The most encountered weak D and partial D variant was type 15 and DFR type, respectively. Conclusions The prevalence of serologically weak D phenotypes varies by race and ethnicity. Turkey is a country covering a mixture of European and Asian DNA with different ethnic groups. Thus, our research as giving the overall distribution of RHD variants from the largest city of Turkey, which may reflect the general ethnic background of the country, would help to the establishment of a databank for blood banking. This paper is the first molecular study on RHD variants in Turkey. New molecular research would be more reliable and precise.

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

BOZKURT, CEYHUN/0000-0001-6771-9894; Atay, Didem/0000-0003-3040-1959; WOS:000400483200002 PubMed: 28267081 The aim of this study was to determine usefulness of measurements of maximal systolic velocity of the hepatic artery with Doppler ultrasonography in the diagnosis of venoocclusive disease (VOD) after hematopoietic stem cell transplantation. We prospectively obtained 5 sonograms per patient: pretransplantation, day + 1, + 7, + 14, and + 28 on 36 nonconsecutive children who underwent hematopoietic stem cell transplantation. We examined the hepatic artery, the portal, hepatic and splenic veins, the thickness of the gallbladder wall, the presence of ascites, and the liver and spleen size. The diagnosis of VOD was based on clinical and laboratory data. Patients were divided into 2 groups: those with VOD (n=18) and those without VOD (n=18). The variance of 2 groups was analyzed. V-max of the hepatic artery had a strong correlation with clinical VOD diagnosis (P

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

Therapeutic plasma exchange (TPE) is an effective treatment method in selective indications. Secondary to access and technical features, it is more difficult to apply in pediatric population than adults. The aim of this study is investigate safety, clinical indications, and results of this method in critically ill pediatric patients who need TPE treatment. All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 4 years (2015-2019) were evaluated retrospectively. TPE procedures (635) were performed for 135 patients. Median age was 34 months (10-108). Ninety-seven patients had mechanical ventilation support. Sepsis with multiple organ failure was the most frequent indication and accounted for 44.4% (n = 60) of the indications followed by hematological and neurological diseases (19.2% and 9.6% respectively). TPE was performed alone in 469 cases (73.9%), in combination with continuous renal replacement therapy in 154 cases (24.2%), and additional to extracorporeal membrane oxygenation in 12 cases (1.9%). Hematological disease and sepsis subgroups had the highest intubation rate, mechanical ventilation period, PRISM score, organ failure count, and mortality. Fresh frozen plasma (FFP) was the most frequently used replacement fluid in 90.4% of the procedures. The most frequent anticoagulant used in TPE was acid citrate dextrose solution (79.3%). Procedural complications were detected in 104 cases (16.3%) and occurred during TPE sessions. Overall survival rate was 78.5%. We found that the non-survivor group had significantly higher rates of organ failures (P = 0.0001), higher PRISM scores on admission (P = 0.0001), and higher rates of invasive ventilation support needed (P = 0.012). TPE is a treatment method which can be safely provided in healthcare facilities with necessary medical and technical requirements. Although it is riskier to provide such treatment to critically ill children, complications can be minimized in experienced healthcare facilities. Overall results are good and can vary depending on indication.

IRIS is a phenomenon describing localized inflammatory reactions at BCG vaccination site and development of lymphadenopathy as immune system recovers. It is a rare entity in children following haploidentical HSCT. We represent the successful treatment of a case with fluctuating lymphadenopathy due to BCG vaccine during immune reconstitution period following ex vivo T-cell-depleted haploidentical HSCT.

PURPOSE: Human Signal transducer and activator of transcription 1 (STAT1) gain of function (GOF) mutations present with a broad range of manifestations ranging from chronic mucocutaneous candidiasis and autoimmunity to combined immunodeficiency (CID). So far, there is very limited experience with hematopoietic stem cell transplantation (HSCT), as a therapeutic modality in this disorder. Here we describe two patients with heterozygous STAT1 GOF mutations mimicking CID who were treated with HSCT. METHODS: Data on the HSC sources, conditioning regimen, graft versus host disease (GvHD) and anti-microbial prophylaxis, and the post-transplant course including engraftment, GvHD, transplant related complications, infections, chimerism, and survival were evaluated. Pre- and post-transplant immunological studies included enumeration of circulating interferon gamma (IFN-γ) - and interleukin 17 (IL-17)-expressing CD4(+) T cells and analysis of IFN-β-induced STAT1 phosphorylation in patient 1 (P1)’s T cells. RESULTS: P1 was transplanted with cord blood from an HLA identical sibling, and P2 with bone marrow from a fully matched unrelated donor using a reduced toxicity conditioning regimen. While P1 completely recovered from her disease, P2 suffered from systemic CMV disease and secondary graft failure and died due to severe pulmonary involvement and hemorrhage. The dysregulated IFN-γ production, suppressed IL-17 response and enhanced STAT1 phosphorylation previously found in the CD4(+) T cells of P1 were normalized following transplantation. CONCLUSION: HSCT could be an alternative and curative therapeutic option for selected STAT1 GOF mutant patients with progressive life-threatening disease unresponsive to conventional therapy. Morbidity and mortality-causing complications included secondary graft failure, infections and bleeding.

ispartof: HAEMATOLOGICA vol:104 issue:8 pages:E335-E339 ispartof: location:Italy status: published

Baris, Safa/0000-0002-4730-9422; kiykim, ayca/0000-0001-5821-3963; FIRTINA, Sinem/0000-0002-3370-8545; Ozen, Ahmet/0000-0002-9065-1901; NG, YUK YIN/0000-0001-9755-6045 Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiencies (PIDs) caused by gene variants that lead to a failure of functional T cell development, with or without accompanying defects in the production of B and/or NK cells Istanbul University Research FundIstanbul University [52575, 20499] This project is supported by Istanbul University Research Fund (No: 52575 and 20499) and Istanbul Bilgi University [Y.Y Ng, 2017)]. WOS: 000463216500006 30903456 Q1

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.

Cytomegalovirus (CMV) infection is one of the most common complications after allogeneic hematopoietic stem cell transplantations (HSCT). Valganciclovir (VGC) has increasingly been used as prophylaxis against CMV infection after solid organ transplantation, but data on the efficacy and safety of VGC in pediatric HSCT patients are limited. We present our experience with VGC following ganciclovir (GCV) as preemptive therapy in pediatric HSCT patients. A total of 46 patients (38% patients) were found to be positive for CMV reactivation. Patients were treated with GCV (group I, n: 22) or GCV followed by VGC (GCV+VGC, group II, n: 24). VGC was preferred in the treatment of outpatients, whereas inpatients were treated with GCV. There was no significant difference in CMV clearance (P=0.78), treatment duration (P=0.087), and second CMV infection (P=0.3) between the 2 groups. The length of hospital stay was 21 days in GCV group, 14 days in VGC following GCV group (P=0.07). There were no treatment-related side effect in both groups. In conclusion, oral administration of VGC as preemptive therapy was found to be safe and effective. It is also a more suitable application for pediatric patients instead of an intravenous route. It could reduce the duration of inpatient stay and cost of hospitalization.

The MN1 (Meningioma 1) gene is overexpressed in certain subtypes of acute myeloid leukemia (AML) and high levels of MN1 expression in mouse bone marrow cells results in myeloid leukemia. We showed that compared with control bone marrow (BM) MN1 expression was increased (2-fold or more) in 29 out of 73 (40%) pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient BM. Additional analysis of MN1 expression in sub-groups within our cohort carrying different chromosome translocations showed that carriers of the good prognostic marker t (12;21)(TEL–AML1) ( n = 27) expressed significantly more MN1 than both healthy controls ( n = 9) ( P = 0.02) and the group carrying the t (9;22)(BCR–ABL) ( n = 9) ( P = 0.001). In addition, AML1 expression was also upregulated in 31 out of 45 (68%) B-ALL patient BM compared with control and there was a significant correlation between MN1 and AML1 expression ( r = 0.3552, P = 0.0167). Retroviral MN1 overexpression increased the colony forming activity of mouse Pro-B/Pre-B cells in vitro . Our results suggest that deregulated MN1 expression contributes to the pathogenesis of pediatric B-ALL. Further investigation into the clinical and biological significance of elevated MN1 expression in TEL–AML1 positive leukemia might provide insight into additional molecular mechanisms contributing to B-ALL and may lead to improved treatment options for patients.

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

Gardner Diamond syndrome is a rare condition characterized with painful ecchymoses in different parts of the body and cutaneous and mucosal hemorrhages. The etiology is not known fully and psychogenic factors are thought to be involved. Cutaneous lesions and hemorrhages develop mostly following emotional stress and rarely minor traumas and may recur. Although the extremities are involved with the highest rate, the lesions may be observed in any part of the body. Hemostatic tests are generally normal. The majority of the subjects is composed of young women. It is observed more rarely in men and children. In this article, a patient who presented with recurring painful echymoses and bleeding disorder and diagnosed with Gardner Diamond syndrome by intracutaneous injection of autologous blood was presented to emphasize that this syndrome is observed rarely in the childhood and should be considered not only in the differential diagnosis of cutaneous lesions, but also in the differential diagnosis of various system hemorrhages.

WOS: 000400127500011, PubMed ID: 28192253, Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range,.5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbiliCal cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 x 10(6) CD 34(+) cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor. (C) 2017 American Society for Blood and Marrow Transplantation.

Oxidant status and antioxidants play important roles in anemias. The present study was conducted to investigate the oxidant-antioxidant status in iron deficiency anemia (IDA), and to evaluate the antioxidant effect of vitamin E in IDA treatment. Ten patients with IDA aged nine months were given only iron treatment, whereas another 10 patients were administered both iron and vitamin E. The complete blood count, plasma malonyldialdehyde (MDA) level, erythrocyte superoxide dismutase level, and the serum vitamin E level, both before and within the treatment phases were examined. The reticulocyte count at the first week of treatment was found lower in the vitamin E-treated group. The mean corpuscular volume (MCV) was found higher in the vitamin E-treated group at the end of therapy. The malonyldialdehyde levels of the group treated with vitamin E were found lower during treatment. These results suggest that iron administration in IDA treatment may stimulate lipid peroxidation, and that vitamin E supplied with iron may reduce the MDA production. The hematological indications of the findings of our study are that the reticulocyte response develops earlier and the microcytosis recovery occurs more rapidly in the vitamin E-administered group in comparison with the group treated with iron only.Serbest radikal reaksiyonları ve antioksidanlar anemi patogenezinde önemli rol oynar. Bu çalışma demir eksikliği anemisi (DEA) tedavisinde oksidan-antioksidan durumu saptamak ve DEA tedavisinde E vitamininin antioksidan etkisini değerlendirmek amacıyla yapılmıştır. Sadece demir tedavisi verilen dokuz aylık 10 hasta ve demir ile birlikte E vitamini tedavisi verilen 10 hasta çalışmaya alınmıştır. Tam kan sayımı, plazma malonildialdehid (MDA) düzeyi, eritrosit süperoksid dismutaz (ESOD) düzeyi ve serum E vitamini düzeyi tedavi öncesi ve tedavi sırasında ölçülmüştür. E vitamini ile tedavi edilen grupta retikülosit sayısı daha düşük bulunmuştur. Ortalama eritrosit hacmi E vitamini ile tedavi edilen grupta tedavinin sonunda yüksek bulunmuştur. Tedavi boyunca MDA düzeyleri E vitamini ile tedavi edilen grupta daha düşük bulunmuştur. Bu sonuçlar DEA tedavisinde verilen demirin lipid peroksidasyonunu uyarabileceğini ve demir ile birlikte verilen E vitamininin MDA üretimini azaltabileceğ ini göstermiştir. Çalışmamızdaki bulguların hematolojik göstergeleri sadece demir verilen gruba göre vitamin E verilen grupta, retikülosit yanıtının daha erken olması ve mikrositozun daha hızlı düzelmesidir.

To study the risk factors for hemangioma-related complications, treatment indications and analyze the outcome of patients with infantile hemangioma. Retrospective. University hospital. Fifty-five patients (1–69 months; median: 12 months) with infantile hemangioma with mean follow-up 19 months. The eligibility was based on the criteria of the International Society for the Study of Vascular Anomalies (ISSVA). The surgical treatment included total excision whereas medical treatment was carried out by interferon and /or corticosteroids. Data was collected including sex, age, prematurity, age at onset, number, anatomic location and size of hemangioma, age at treatment, cause of treatment decision, family history, presence of extra malformations, involvement of internal organs, presence of life altering or life threatening complications, response to treatment, dose and duration of medications, complications associated with treatment, follow-up period, and final outcome. Thirty-four (62%) patients were followed-up without treatment, whereas 21 others underwent treatment including steroids, interferon, and surgery. The size of hemangioma was a major factor that predicted hemangioma-related complications (P=0.002). Patients with hemangioma related complications had bigger lesions (size ≥40cm2 or the longest size on a single plane ≥5 cm). Nineteen patients (34%) had complications, but only 8 (14.5%) out of them had life or function-threatening complications. Although dosing and treatment protocol is still debatable, steroids and interferon are good options for hemangioma treatment. The management strategy should be individualized for each case.

Despite the introduction of new broad-spectrum antibiotics and antifungal therapies over the past decade, infections remains the most frequent cause of death in patients with neutropenia. The aim of this study is to assess the effect and safety of granulocyte transfusions (GTX) for the treatment of severe life-threatening infections in pediatric patients with febrile neutropenia or defective granulocyte functions.In this study, 35 pediatric patients with high-risk febrile neutropenia or defective granulocyte functions, who received 111 GTX, were included. GTX were used for 3 consecutive days during infections not responding to antimicrobial therapy.The mean granulocyte content per concentrate was 27.4×10⁹ (min: 4.2×10⁹ to max: 68.4×10⁹) depending on donor's white blood cell count before harvest. GTX were well tolerated in all patients. The infection-related survival rate was 82.4% and overall survival rate was 77.1% at day 30. The overall survival rate was 65.7% and 52% at 3 and 48 months, respectively.GTX is safe and effective in controlling the life-threatening infections. Further randomized controlled studies with long-term follow-up are needed to assess the exact role of GTX in the outcome of patients with neutropenia and patients with defective granulocyte functions.

Received/Gelis tarihi : September 3, 2013 Accepted/Kabul tarihi : November 16, 2013 To the Editor, Although clofarabine is known as an effective novel agent in relapsed acute leukemia [1,2,3,4,5], determining the optimum combination with other agents and the optimum time to use remains a challenge. Clofarabine is recommended to be used after 2 protocol regimens in patients with relapsed leukemia [1]. We want to add our experience with clofarabine in children with multi-relapsed acute lymphoblastic and myeloblastic leukemia. We analyzed the data of 12 children (1-13 years old) treated with the CLOVE protocol [clofarabine (4 mg/m2), cyclophosphamide (440 mg/m2), and etoposide (100 mg/m2) for 5 days] [2,3,4] for relapsed or refractory acute leukemia between 2009 and 2013. We used this therapy in a third or more of cases of relapsed acute leukemia. Bone marrow relapses were eligible for the treatment protocol. Seven of 12 patients had acute lymphoblastic leukemia (ALL) and 5 had acute myeloid leukemia (AML) (Table 1). Patients with relapsed ALL were treated with 1 or 2 cycles of FLAG after applying the BFM-95 REZ protocol. Patients with no response were administered clofarabine. Patients with relapsed AML were treated with 2 cycles of FLAG after applying the MRC protocol. Patients without response were given clofarabine in 1 or 2 cycles. The required permission for all patients was received from the Ministry of Health.

T-cell-depleted HAPLO HSCT is an option to treat children with high-risk acute leukemia lacking an HLA-identical donor. We reviewed the outcome of children with acute leukemia after HAPLO (n = 21) and HLA-MUD (n = 32) transplantation. The proportion of patients with ≥CR2 was significantly higher in HAPLO transplantation than MUD transplantation. Patients with MUD transplantation were significantly higher ABO incompatible than patients with HAPLO transplantation. There was no difference between the 2 groups in terms of engraftment, aGvHD and cGvHD, VOD, hemorrhagic cystitis, infections, and relapse. The 5-year OS of MUD transplantation and HAPLO transplantation groups was found 65.8% and 71.1%, respectively (log-rank 0.51). The 5-year RFS was 80.7% for MUD transplantation group and 86.9% for HAPLO transplantation group (log-rank 0.48). There was no statistically significant difference between 2 groups according to TRM (25% MUD transplantation vs 16.3% HAPLO transplantation, log-rank 0.48). These data suggest that survival for patients with high-risk acute leukemia after HAPLO transplantation with ex vivo ɑβ+ T-cell depletion is comparable with MUD transplantation.

Development of KS in pediatric liver transplant recipients is a rare entity and has dismal prognosis. Latent HHV-8 infection, immunosuppression, and genetic predisposition are possible etiological factors. Decreasing the dose or cessation of immunosuppressive drugs, switching to sirolimus with antiproliferative and antitumor properties, and different chemotherapeutic regimens are the current therapeutic strategies. We herein report a pediatric liver transplant recipient who developed generalized KS at post-transplant fifth month. The disease had an aggressive course despite the highly toxic chemotherapy. On the other hand, a prompt and durable response was provided by paclitaxel with tolerable side effects. The patient is now free of disease for at least 24 months and healthy with good graft function under sirolimus therapy as maintenance immunosuppression. Instead of highly toxic chemotherapy, paclitaxel can be used as therapeutic option in cases with generalized disease and in those who are unresponsive to conventional chemotherapy. However, new studies are needed to assess the efficacy of the paclitaxel therapy in KS in the liver transplant recipients.

Background Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy with or without autologous/allogeneic hematopoetic stem cell transplantation (HSCT). There have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients. Methods Two RSV infection outbreaks developed between February–April 2006 and January–March 2009 in hospitalized pediatric patients for various hemato-oncological diseases ± HSCT. A survey of respiratory viruses was done using direct immunofluorescent antibody assay from nasopharyngeal washing aspirate. Results In two RSV infection outbreaks (2006 and 2009), RSV antigen was detected in 6/30 patients. Five of six patients with RSV antigen were all treated with 0.2–0.4 g/kg intravenous immune globulin (IVIG) and specific antiviral therapy, oral ribavirin (20–25 mg/kg/day in three doses). Five patients recovered fully, although two were retreated due to recurrent (+) RSV antigen and respiratory symptoms within 2 weeks. We did not give oral ribavirin to one patient with (+) RSV antigen due to mild symptoms. All patients are alive and well. Conclusions In contrast with the outcome of RSV infection in adult oncology patients, the mortality associated with RSV infection in pediatric oncology patients even in post bone marrow transplantation (BMT) period, is low when diagnosed and treated early enough. Oral ribavirin might be an option together with IVIG in the treatment of RSV especially when other forms of antivirals could not be obtained. This approach will make it possible to give the scheduled anti-neoplastic therapy on time. Pediatr Pulmonol. 2010; 45:307–311. © 2010 Wiley-Liss, Inc.

Granulocyte colony-stimulating factor (G-CSF) is widely used to reduce the risk of infection resulting from neutropenias and to mobilize and collect CD34+ hematopoetic progenitor cells (HPCs) for autologous and allogenic transplantation. The safety of recombinant human G-CSF (rhG-CSF) administration in healthy donors has been investigated in several studies. However, there are limited cumulative data about the effects of rhG-CSF on hemostasis. Hemostatic parameters, including urokinase-type plasminogen activator antigen (u-PA:Ag) and nitric oxide in 17 healthy granulocyte apheresis donors who donated for neutropenic patients were evaluated. rhG-CSF (single dose, 10 μg/kg subcutaneously) and dexamethasone (8 mg, single dose oral) were given to donors 12 hours before granulocyte apheresis. Two blood samples were drawn at time 0 (T0) before rhG-CSF and dexamethasone administration and at time 1 (T1), immediately before the apheresis. A statistically significant rise in coagulant factor VIII (FVIII) and von Willebrand factor (vWF), and slightly rise in u-PA:Ag were observed after G-CSF plus dexamethasone administration. In addition, there were positive correlations between vWF-D-dimer and FVIII-D-dimer. A significant decrease in mean total nitric oxide (NOx), nitrite, and nitrate levels was also found after G-CSF plus dexamethasone administration. Moreover, there was a strong negative correlation between nitrite and D-dimer levels ( r = −0.611; P = .009). Even if partially compensated with u-PA and protein C, increased FVIII and vWF activity, and decreased nitric oxide levels may still partially contribute to progress of thrombosis risk in rhG-CSF plus dexamethasone administered healthy granulocyte donors. Large numbers of healthy donors exposed to G-CSF plus dexamethasone will be needed to evaluate the risk of thrombosis in this population.

The plasminogen (Plg) protein is the inactive proenzyme form of plasmin that dissolves fibrin thrombi by a process called fibrinolysis. It has been shown that homozygous or compound-heterozygous deficiency of this protein is a major cause of a rare inflammatory disease affecting mainly mucous membranes found in different body sites. In this study, five individual Turkish patients and nine Turkish families with type 1 Plg deficiency were investigated for PLG gene mutations. All of the coding regions of the PLG gene mutations were screened for mutations using denaturing high-pressure liquid chromatography (DHPLC). Samples showing a different DHPLC profile were subjected to DNA sequencing analysis. Here, we described five novel mutations namely, Cys49Ter, +1 IVS6 G>A, Gly218Val, Tyr283Cys, and Gly703Asp. Previously identified five nonsynonymous (Lys38Glu, Glu180Lys, Gly420Asp, Asp453Asn, Pro763Ser), five synonymous (330 C>T, 582 C>T, 771 T>C, 1083 A>G, 2286 T>G), and a 3' untranslated region (3' UTR) mutation (c.*45 A>G) were also reported in this present study. In this study, we have identified a total of eight mutations, five of which are novel. The mutations/polymorphisms identified in eight of the patients do not explain the disease phenotype. These cases probably carry other pathological mutations (homozygous or compound heterozygous) that cannot be detected by DHPLC. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

This study evaluated the efficacy of mesenchymal stem cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. We report the first experience using MSCs to treat refractory aGVHD in 33 pediatric patients undergoing allogeneic HSCT from Turkey. Totally, 68 doses of bone marrow derived MSCs were infused. The median dose of MSC was1.18×106cells per kg body weight. Overall, complete response (CR) was documented in 18 patients, partial response (PR) was documented in 7 patients, and no response (NR) was documented in 8 patients. The 2-year estimated probability of overall survival (OS) for patients achieving CR and PR/NR was 63.8% and 29.4%, respectivelyp=0.0002. While the cumulative incidence of transplant related mortality (TRM) at day 100 after first MSC infusion was 46.6% in PR/NR patients, there was no any TRM at day 100 after first MSC infusion in CR patientsp=0.001. Twelve patients developed chronic GVHD (cGVHD); eight of them were alive, with five having extensive disease and three having limited disease. In conclusion, MSCs appear to be safe and effective treatment option for pediatric patients with steroid refractory aGVHD. But the efficacy of MSCs on cGVHD in aGVHD patients treated with MSCs seems to be limited.

A 15-year-old Iraqi male patient with acute lymphoblastic leukemia received an allogeneic bone marrow transplant from his brother. On the 18th day after the transplant, the patient developed grade II acute graft-versus-host disease, and treatment included methylprednisolone. On day 140, the patient was diagnosed with leukoderma. On day 150, the patient was admitted to hospital because of numbness and muscle weakness in the extremities and a disturbance of the gait. Neurologic examination showed muscle weakness in the upper and lower extremities and there were no deep tendon reflexes. Nerve conduction studies showed reduced conduction speeds of the motor nerves with demyelinating features. The patient was diagnosed as having a chronic inflammatory demyelinating polyradiculoneuropathy (CIDB) based on clinical and electrophysiological findings. Treatment included methylprednisolone and intravenous immunoglobulin. The neurologic function improved but the skin lesions persisted. This case shows that graft-versus-host disease can act as a triggering factor for the appearance of autoimmune diseases. Keywords : Leukemia, Graft-versus-host disease, Leukoderma, Chronic inflammatory demyelinating polyneuropathy

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.

The ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic HSCT. Nevertheless, conflicting data still exist about the influence of ABO incompatibility on transplant outcome in pediatric patients with thalassemia. Fifty-one children with beta-thalassemia major who underwent allogeneic HSCT were enrolled this study. Twenty-three of them (45%) received an ABO-incompatible transplant [minor ABO mismatch: six (26%), major ABO mismatch: fourteen (61%), and bidirectional mismatch: three (13%)]. In this study, ABO incompatibility did not significantly impair GVHD, VOD, neutrophil and platelet engraftment, TRM, OS and TFS. Particularly in major and bidirectional ABO-mismatched patients, a delayed erythroid recovery was recorded as compared to the group receiving an ABO-compatible graft (median time, 31 and 38 days vs. 19.5 days; p: 0.02 and p: 0.03). Median time to red cell transfusion independence was significantly longer in major ABO-incompatible patients (median time, 87 days vs. 32 days; p: 0.001). Therefore, whenever feasible, major ABO-mismatched donors should be avoided in HSCT recipients, to prevent delayed erythroid recovery with prolonged RBC transfusion needs and impaired quality of life.