Outcomes of HLA-mismatched HSCT with TCRαß/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity.

ABSTRACT: HLA-mismatched transplants with either in vitro depletion of CD3+ T-cell receptor (TCR)αß/CD19 (TCRαß) cells or in vivo T-cell depletion using posttransplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEIs). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEIs undergoing their first transplant between 2010 and 2019 from an HLA-mismatched donor using TCRαß (n = 167) or PTCY (n = 139). The median age for hematopoietic stem cell transplantation (HSCT) was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84) after TCRαß and 66% (57-74) after PTCY (P = .013). Pre-HSCT morbidity score (hazard ratio [HR], 2.27; 1.07-4.80, P = .032) and non-busulfan/treosulfan conditioning (HR, 3.12; 1.98-4.92, P < .001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50%-66%) after TCRαß and 57% (48%-66%) after PTCY (P = .804). The cumulative incidence of severe acute graft-versus-host disease (GvHD) was higher after PTCY (15%, 9%-21%) than TCRαß (6%, 2%-9%, P = .007), with no difference in chronic GvHD (PTCY, 11%, 6%-17%; TCRαß, 7%, 3%-11%, P = .173). The 3-year GvHD-free EFS was 53% (44%-61%) after TCRαß and 41% (32%-50%) after PTCY (P = .080). PTCY had significantly higher rates of veno-occlusive disease (14.4% vs TCRαß 4.9%, P = .009), acute kidney injury (12.7% vs 4.6%, P = .032), and pulmonary complications (38.2% vs 24.1%, P = .017). Adenoviremia (18.3% vs PTCY 8.0%, P = .015), primary graft failure (10% vs 5%, P = .048), and second HSCT (17.4% vs 7.9%, P = .023) were significantly higher in TCRαß. In conclusion, this study demonstrates that both approaches are suitable options in patients with IEIs, although they are characterized by different advantages and outcomes.

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

The impact of Treosulfan-based conditioning for inborn errors of immunity: Is dose monitoring crucial?

INTRODUCTION: In children with inborn errors of immunity (IEI) who will receive a hematopoietic stem cell transplant (HSCT) treosulfan-based conditioning is currently preferred. The aim of this study was to investigate early and late outcomes in pediatric IEI patients receiving pre-HSCT treosulfan and to examine the effect of treosulfan dose monitoring on outcomes. METHODS: Seventy-three pediatric patients receiving this management between 2015 and 2022 were included. RESULTS: Overall survival rate was 80%, and event-free survival was 67.8%. A larger treosulfan dose AUC after first application increased the rate of early toxicity (p = .034) and slowed lymphocyte engraftment (r = .290; p = .030). Underlying disease, treosulfan AUC, donor type, stem cell type, number of immunosuppressive agents, the dose of anti-thymocyte globulin, and post-transplantation cyclophosphamide did not to increase risk of acute graft-versus-host disease. The risk of mixed chimerism (MC) in patients with autoimmune lymphoproliferative syndrome and leukocyte adhesion deficiency were higher than those with severe combined immunodeficiency (p = .021 and p = .014, respectively). The risk of MC was lower in those receiving peripheral blood stem cells (SC) compared with bone marrow derived SC (OR = .204, p = .022). CONCLUSION: The AUC of the treosulfan dose was not associated with poorer late outcomes. Treosulfan is an agent that can be used safely in the IEI patient group,  level measurement appears essential to identify early toxicities. Prospective studies with more extended follow-up periods are needed.

Evaluation of the risk factors for BK virus-associated hemorrhagic cystitis in pediatric bone marrow transplantation patients: Does post-transplantation cyclophosphamide increase the frequency?

BACKGROUND: BKV-HC is one of the most significant complications of HSCT. This retrospective study aimed to determine the frequency of BKV-HC in pediatric patients undergoing HSCT, detect the associated risk factors for the development of BKV-HC, and explore the effects of post-transplantation Cy use. METHODS: Three hundred twenty-seven patients (girls: 121, boys: 206) were analyzed according to sex, conditioning regimen, transplantation type, donor relatedness, stem cell source, the presence and grade of aGVHD, CMV co-existence, and Cy use. RESULTS: Multivariate analysis confirmed the prognostic importance of age (OR: 4.865), TBI use, the presence of aGVHD (OR: 2.794), CMV coinfection (OR: 2.261), and Cy use (OR: 27.353). A statistically significant difference was found between the mean BKV-HC follow-up times compared with post-transplantation Cy intake (p < .001). The BKV-HC rate increased as the number of risk factors of the patient increased. CONCLUSION: BKV-HC is an essential complication of HSCT primarily associated with Cy use, the presence of aGVHD, and donor relatedness. The present study shows that the use of Cy in the post-transplantation period further increases BKV-HC risk in pediatric patients, regardless of dose.

The Inhibitory Effects of Amylase and Streptokinase on Minimum Inhibitory Concentration of Antibiotics Used to Treat Gram Negative Bacteria Biofilm Infection on Indwelling Devices.

The study evaluated and compared the effect of adding streptokinase and amylase to antibiotics that are already used in clinical practice to treat Gram negative bacteria biofilm infection on indwelling devices on the antibiotics' minimum inhibitory concentration (MIC). 24 h-old biofilms were developed on 96-well plate with eight clinical isolates. MIC of amikacin, cefepime, ceftazidime, colistin, meropenem, and piperacillin-tazobactam, on biofilms were measured before and after the addition of 25 U/ml streptokinase and 25 µg/ml amylase with microplate reader. The addition of streptokinase reduces the MICs of cefepime, ceftazidime, colistin, meropenem from (16, 16, 8, 4 µg/ml) to (8, 1, 1, 0.5 µg/ml) in Escherichia coli (isolate 1). While the addition of amylase reduces the MICs of only cefepime, ceftazidime from (16, 16 µg/ml) to (2, 4 µg/ml) in E. coli (isolate 1). In Pseudomonas aeruginosa (isolate 4), the MICs of amikacin, cefepime, ceftazidime, colistin and meropenem (64, 16, 32, 4, 32 µg/ml) reduced to (2, 1, 0.5, 0.25, 0.5 µg/ml) with streptokinase and (4, 4, 4, 2, 0.5 µg/ml) with amylase respectively. Similar inhibitions were seen in Pseudomonas putida, Proteus mirabilis. We can conclude that the addition of streptokinase and amylase were effective in reducing the MICs of antibiotics that are commonly used to treat Gram negative bacteria biofilm infection on indwelling devices, thereby increasing susceptibility of bacteria to antibiotics. Streptokinase obviously had a greater effect than amylase, implying that it should be prioritized in future in vivo and clinical studies to obtain successful therapy with antibiotics on biofilm infections.

Busulfan-fludarabine- or treosulfan-fludarabine-based myeloablative conditioning for children with thalassemia major.

Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients' life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfan-fludarabine-based and treosulfan-fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan-fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan-fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3-95.1%) after busulfan-fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7-96.6%) after treosulfan-fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

Primary immunodeficiencies: HSCT experiences of a single center in Turkey.

BACKGROUND: Primary immunodeficiency diseases (PID) are characterized by the occurrence of frequent infections and are caused by many genetic defects. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for the majority of PID. As a Pediatric Hematology-Oncology-Immunology Transplantation Unit, we wanted to present our HSCT experience regarding treatment of primary immunodeficiency diseases. METHODS: 58 patients were included in the study between January 2014 and June 2019. We searched 9/10 or 10/10 matched-related donor (MRD) firstly, in the absence of fully matched-related donor. We screened matched unrelated donor (MUD) from donor banks. MRD was used in 24 (41.3%) patients, MUD in 20 (34.4%) patients, and haploidentical donors in 14 (24.1%) patients. Demographic data, HSCT characteristics, and outcome were evaluated. While 16 patients had severe combined immunodeficiency (SCID), the remaining was non-SCID. RESULTS: Of the 58 patients, 38 were male and 20 were female. Median age at transplantation was 12 months (range: 2.5-172 months). Combined immunodeficiencies consisted 67.2% of patients. Mean follow-up time was 27 months (6 months-5 years). Median neutrophil, lymphocyte, and thrombocyte engraftment days were similar in comparison of both donor type and stem cell source. The most common complication was acute GvHD in 15 (25.8%) patients. In total, five patients (31%) belonging to the SCID group and 10 patients (23.8%) belonging to the non-SCID group died. Our total mortality rate was 15 (25.8%) in all patients. CONCLUSIONS: We would like to present our HSCT experiences as a pediatric immunology transplantation center. Existing severe infections before transplantation period, BCGitis, and CMV are important issues of transplantation in Turkey. However, the follow-up time is shorter than some studies, our results regarding complications and survival are similar to previous reports.

Prognostic factors for survival in children who relapsed after allogeneic hematopoietic stem cell transplantation for acute leukemia.

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.

Are the Anxiety Levels of Pediatric Hematology-Oncology Patients Different From Healthy Peers During the COVID-19 Outbreak?

The COVID-19 outbreak has caused anxiety among children with hematology-oncology disease and their families, as it has in every segment of society. In this study, we aimed to detect the anxiety levels of children with hematologic or oncologic disease and of their parents after the COVID-19 outbreak. The sample consisted of 15 patients 12 to 18 years of age receiving treatment in the Pediatric Hematology and Oncology Unit in Altinbas University Medical Faculty Bahçelievler Medikalpark Hospital and 33 parents of the same unit patients between 6 and 18 years of age, and their 35 healthy peers and their parents. The State-Trait Anxiety Inventory was applied to participant children and their parents to evaluate their general anxiety and pandemic-related anxiety levels. Children with a hematology-oncology disease and their families were compared with healthy peers and their families. No significant difference was observed for pandemic-related anxiety levels (P>0.05). Both parent groups exhibited higher anxiety levels with regard to the pandemic than did their children (P<0.05). Children with hematology-oncology disease reported significantly higher trait anxiety levels when compared with healthy peers (P=0.01). The families of children who had not received stem cell transplantation had higher state and trait anxiety scores than the families of children who had received the transplantation (P<0.05). Even though they were in the high-risk group, children with a hematology-oncology disease and their families had pandemic-related anxiety levels comparable with those of healthy peers and their families.

Comparison of Hematopoietic Stem Cell Transplantation Results in Patients with ß-Thalassemia Major from Three Different Graft Types.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the curative therapy for ß-thalassemias that induces severe life-threatening complications. The human leukocyte antigen (HLA) registries and umbilical cord blood banks have carried out diligent searches to find matched unrelated donors (MUDs) for about 70.0% of patients from 2000 onwards. The chance of finding a non-sibling fully matched family donors is higher in some ethnic groups in which consanguineous marriages are common. We have studied and compared transplant complications and outcomes in different graft types (sibling, non-sibling family and unrelated). The non-sibling matched family donor (MFD) group consisted of four mothers, three fathers, five cousins, one paternal uncle and one paternal aunt. There was no significant difference in the mean transfused CD34+ cells, engraftment, median days of neutrophil and platelet recovery were achieved (p > 0.05). The distribution of postttransplant complication did not show any significant difference between groups (p > 0.05). In univariate analysis and multivarite analyses, age, gender, Pesaro risk group (I-II vs. III) and ABO incompatibilty demonstrated a significant difference in disease free survival (p < 0.05). Furthermore, in the second step of investigating overall survival (OS), age, gender and Pesaro risk group (I-II vs. III) showed a significant difference (p < 0.05). There was no significant difference in transplant-related mortality (TRM) between groups. Non-sibling related donor transplants are important for populations where consanguineous marriages are common. Transplant groups according to graft type had similar thalassemia-free survival (TFS) and OS when using a treosulfan-based regimen in our study.

Invasive Saprochaete capitata Infection in a Patient with Autosomal Recessive CARD9 Deficiency and a Review of the Literature.

PURPOSE: Autosomal recessive (AR) CARD9 deficiency is an inherited immune disorder which results in impaired innate immunity against various fungi. Superficial and invasive fungal infections, mainly caused by Candida or Trichophyton species, are the hallmark of CARD9 deficiency. Together with the increasing number of CARD9-deficient patients reported, different pathogenic fungal species have been described such as Phialophora, Exophiala, Corynespora, Aureobasidium, and Ochroconis. Saprochaete capitata is an opportunistic infectious agent in immunocompromised patients and is a common cause of invasive fungal disease in patients with hematological malignancies. In this study, we investigated the causative genetic defect in a patient with S. capitata fungal infection which disseminated to lymph nodes and common bile duct. METHODS: The identification of the isolated yeast strain was made by direct microscopic examination and confirmed by internal transcribed spacer (ITS) sequencing. We applied whole exome sequencing to search for the disease-causing mutation. Sanger sequencing was used to validate the mutation in the patient and his parents. RESULTS: S. capitata was isolated from the biopsy specimen as the causative microorganism responsible for the invasive fungal disease in the patient. Whole exome sequencing revealed a homozygous c.883C > T, (p.Q295*) mutation in CARD9, confirmed by Sanger sequencing. CONCLUSIONS: This is the first report of invasive Saprochaete infection associated with autosomal recessive (AR) CARD9 deficiency in the literature and thereby further extends the spectrum of fungal diseases seen in these patients.

Hematopoietic Stem Cell Transplantation Using Preimplantation Genetic Diagnosis and Human Leukocyte Antigen Typing for Human Leukocyte Antigen-Matched Sibling Donor: A Turkish Multicenter Study.

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 × 106 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.

Invasive fungal infections in children with hematologic and malignant diseases.

BACKGROUND: To evaluate the clinical feature and outcome of invasive fungal infections (IFI) in children with hematologic and malign diseases. PATIENTS AND METHODS: The medical records of children with hematologic and malignant diseases, who were hospitalized at our hospital between January 2010 and December 2011, were reviewed. Proven, probable, and possible IFIs were diagnosed according to the revised definitions of the European Organization for Research and Treatment of Cancer/Mycosis Study Group. The demographic, clinical, and laboratory characteristics of the patients who met the study criteria were evaluated. RESULTS: IFI was diagnosed in 67 (7.2%) febrile episodes of 56 patients, of which 10 (1.2%) were proven, 20 (2%) probable, and 37 (4%) possible IFI. Blood culture of 10 cases with proven IFI yielded yeast and the most common isolated agent was Candida parapsilosis. Seventy percent of cases with fungemia had central venous catheter (CVC). Twenty cases with probable IFI had invasive mold infection. The cases with mold infection had higher median C-reactive protein values, lower neutrophil counts, and longer duration of neutropenia compared with the cases with yeast infection. A total of 14 patients (20.9%) died. Presence of CVC, bone marrow transplantation, total parenteral nutrition, prolonged fever, and proven/probable IFI were detected more often in patients who died, compared with patients who survived. CONCLUSIONS: IFIs are important causes of death in children with hematologic and malignant diseases. Mold infections are seen more frequently in cases with prolonged and profound neutropenia, and invasive yeast infections, especially with non-albicans Candida species, in cases with CVC. Early and effective treatment considering these findings will help to decrease the mortality.

Epidemiologic and microbiologic evaluation of catheter-line bloodstream infection in a pediatric hematopoietic stem cell transplant center.

BACKGROUND: Children who underwent hematopoietic stem cell transplant (HSCT) transplants are at high risk of developing central-line-associated bloodstream infections (CLABSIs). The present study aimed to identify possible risk factors for mortality by analyzing the clinical and laboratory characteristics of patients diagnosed with CLABSI in our pediatric hematopoietic stem cell transplant unit. METHODS: The initial CLABSI episodes of 102 children were analyzed. Medical records of the patients were evaluated by preformed standardized surveys. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for mortality. RESULTS: Thirty-five patients (34.3%) were female. The median age was 48 months (3-204). The median time to onset of CLABSI was 19 days (4-150). The gram-negative and gram-positive bacteria ratio among the causative agents was 57.8% to 34.3%. The mortality rate was 12.6%. The presence of severe neutropenia, initiation of inappropriate empirical antibiotic therapy, the presence of hypotension, persistent bacteremia, pediatric intensive care unit admission, growth of carbapenemase-positive gram-negative microorganism and multidrug-resistant bacteria were significantly high in the mortality group when compared to survivors. The presence of hypotension, inappropriate empirical antibiotic therapy, and persistent bacteremia were found to be independent risk factors for mortality. CONCLUSIONS: Rational use of antibiotics, active surveillance and screening of patients together with improved infection control practices may reduce the incidence and the consequences of CLABSIs.

Hemophagocytic bone marrow aplasia with plasma cells in a RAG2-deficient SCID case after a nonconditioned transplantation from a fully matched sibling.

We report a RAG2-deficient patient with severe combined immunodeficiency and hemophagocytic bone marrow aplasia with plasma cells after a nonconditioned transplantation from a fully matched sibling. After engraftment, disseminated BCGosis appeared because of graft versus host disease prophylaxis. On the 55th day, eosinophilia, neutropenia, and thrombocytopenia developed. Aplasia, hemophagocytic histiocytes, and plasma cells were found on his bone marrow with very high level of serum immunoglobulin E. We could not discriminate exactly whether BCGosis or alloimmune response is the cause of hemophagocytic aplasia with plasma cells. Despite the second hematopoietic stem cell transplantation with a reduced intensity conditioning regime, his marrow aplasia did not recover and he died. This case suggests that BCGosis might be associated with hemophagocytic marrow aplasia with plasma cells in an alloimmune reaction.

t(6;9)(p23;q34) presenting acute myeloid leukemia in a child with an unsuspected 45,X/46,X,derY [?t(Yp;Yq)] chromosomal constitution: yet another Y chromosome overdosage and malignancy association.

Development of leukemia in patients with sexual chromosome abnormalities is relatively rare and mostly involves cases of monosomy X, Turner syndrome. Here, we report on a child having a 45,X/46,X,derY [?t(Yp;Yq)] chromosomal constitution (variant Turner syndrome) presenting with concordant acute myeloid leukemia and a rarely seen clonal neoplasic cell lineage-related karyotype, t(6;9)(p23;q34).

Rare coagulation disorders: a retrospective analysis of 156 patients in Turkey.

OBJECTIVE: To retrospectively evaluate the clinical findings, laboratory data, management, and outcome in a group ofTurkish children diagnosed with rare coagulation deficiencies (RCDs) between January 1999 and June 2009. MATERIAL AND METHODS: The Turkish Society of Pediatric Hematology-Hemophilia-Thrombosis-Hemostasissubcommittee designed a Microsoft Excel-based questionnaire for standardized data collection and sent it to participatinginstitutions. RESULTS: In total, 156 patients from 12 pediatric referral centers were included in the study. The cost common RCDswere as follows: FVII (n = 53 [34%]), FV (n = 24 [15.4%]), and FX (n = 23 [14.7%]) deficiency. The most common initialfinding in the patients was epistaxis, followed by ecchymosis, and gingival bleeding. CONCLUSION: Initial symptoms were mucosal bleeding, and fresh frozen plasma (FFP) and tranexamic acid werethe most commonly used treatments. We think that prophylactic treatment used for hemophilia patients should beconsidered as an initial therapeutic option for patients with rare factor deficiencies and a severe clinical course, and forthose with a factor deficiency that can lead to severe bleeding.