Prognostic Role of Postinduction Minimal Residual Disease and Myeloid Sarcoma Type Extramedullary Involvement in Pediatric RUNX1-RUNX1T1 (+) Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia with the t(8;21)(q22;q22) rearrangement (RUNX1-RUNX1T1 (+) AML) is known to have a favorable prognosis. Our study aimed to determine the most important prognostic variables among an aggregate of clinical, genetic, and treatment response-based factors in pediatric RUNX1-RUNX1T1 (+) AML. MATERIALS AND METHODS: We analyzed the characteristics and outcome of 40 patients who were diagnosed with and treated for RUNX1-RUNX1T1 (+) AML from April 2008 to December 2016 at our institution. RESULTS: A<-2.2 log fusion transcript decrement after remission induction, myeloid sarcoma type extramedullary involvement (EMI) at diagnosis, higher initial white blood cell count, and presence of KIT mutation predicted lower event-free survival. Both lower fusion transcript decrement after remission induction and the presence of EMI at diagnosis proved to be significant adverse factors in the multivariate study. The 5-year event-free survival was 70.0±7.2% (28/40); 8 of the 12 relapsed patients survive disease-free, resulting in 5-year overall survival of 89.5±5.0% (36/40). CONCLUSIONS: Kinetics of response to remission induction chemotherapy, measured in terms of the PCR value for the fusion transcript, and the presence of myeloid sarcoma type EMI at diagnosis may predict the risk of relapse in pediatric RUNX1-RUNX1T1 (+) AML.

Treatment of children with acute lymphoblastic leukemia with risk group based intensification and omission of cranial irradiation: A Korean study of 295 patients.

BACKGROUND: Recent studies indicate 70-80% event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL). In this study, we report the outcome of 295 children and adolescents treated at our institution, with stratification into four risk groups, and omission of cranial irradiation in all patients. PROCEDURE: Patients were diagnosed from January 2005 to December 2011 and classified and treated as low, standard, high, and very high risk groups. A delayed intensification phase was given twice for high and very high risk groups. None of the patients received cranial irradiation for central nervous system (CNS) prophylaxis. RESULTS: The 10-year EFS and overall survival (OS) were 78.5 ± 2.5% and 81.9 ± 2.7%, respectively. EFS according to risk group was as follows: low risk 91.2 ± 3.7%, standard risk 98.1 ± 1.9%, high risk 81.5 ± 4.3%, very high risk 59.4 ± 5.3%. In a multivariate analysis, high hyperdiploidy and infant ALL were significant predictors of EFS. Cumulative incidence of any relapse, isolated CNS relapse, and any CNS relapse were 17.1 ± 2.3%, 1.5 ± 0.7%, and 2.3 ± 0.9%, respectively. Other events included infection-related deaths during remission induction chemotherapy (3), primary refractory disease (2), and treatment-related deaths in first complete remission (8). CONCLUSIONS: In this single-institution study of Korean pediatric ALL patients, risk group based intensification with omission of cranial irradiation resulted in EFS comparable to previous studies, excellent survival of low- and standard-risk patients, and a low rate of CNS relapse.

Treatment of children with acute myeloid leukaemia who relapsed after allogeneic haematopoietic stem cell transplantation.

Despite improvements in diagnosis and treatment, 30-40% of children with acute myeloid leukaemia (AML) experience relapse. For those who relapse after allogeneic haematopoietic stem cell transplantation (allo-HSCT), the prognosis is particularly poor, with limited reported literature on these patients. We reviewed the clinical course of 49 children with AML (28 males, 21 females) who received allo-HSCT between 1993 and 2011, and who had subsequently relapsed. Study endpoints included (i) complete remission (CR) rate after intensive chemotherapy, and prognostic factors for CR, (ii) disease-free survival (DFS) and overall survival (OS) for patients who achieved CR and (iii) OS for recipients of intensive chemotherapy and prognostic factors for OS. Of the 36 patients who received intensive chemotherapy after post-HSCT relapse, 26 (72%) achieved CR. For patients who achieved CR, 5-year DFS and OS were 32·6 ± 10·2% and 44·4 ± 11·1%, respectively. For all recipients of intensive chemotherapy, 5-year OS was 31·6 ± 8·7%. Cumulative incidence of treatment-related death was 14·4%. All three recipients of second HSCT died. Amongst prognostic factors predicting improved survival, only disease status at HSCT (early first CR vs. others) proved significant in multivariate study (Hazard Ratio 2·42, 95% Confidence Interval 1·02-5·74, P = 0·045). Treatment with curative intent was able to salvage a minor but important subset of children with AML who relapsed post-allogeneic transplant.

Reduced dose cyclophosphamide, fludarabine and antithymocyte globulin for sibling and unrelated transplant of children with severe and very severe aplastic anemia.

We evaluated the results of a novel conditioning regimen of reduced dose cyclophosphamide (Cy, 25 mg/kg for four days), fludarabine (Flu, 30 mg/m(2) for four days), and rabbit ATG (2.5 mg/kg for three days) for allogeneic transplant of children with SAA, implemented since January 2009. Overall, 23 patients were treated with this regimen (16 male, seven female), including 10 diagnosed with VSAA. Donors included eight-MSD and 15 UD (five-matched UD, and 10 mismatched UD). All patients showed neutrophil and platelet engraftment. Cumulative incidence of acute (grade 2 or above) and chronic GVHD was 26.1% and 8.7%, respectively. Estimated two-yr FFS and OS for the entire cohort was 90.3 ± 6.5%. Rates of TRM and graft failure were 5.3% and 4.3%, respectively. No difference in OS was found according to disease severity (SAA vs. VSAA, p = 0.184), or according to donor type (MSD vs. UD, p = 0.699). Excellent outcomes of patients with VSAA underscore the efficacy of allogeneic transplant as a means of expediting hematopoietic recovery. Improved survival of UD transplant reaffirms its role as a valid therapeutic alternative in the absence of MSD.

Valproate-induced panhypogammaglobulinemia.

Valproate is one of the most used anti-epileptic drugs. Its common side effects are nausea, vomiting, weight gain, hair loss, tremor, changes in behavior, slowed thinking and impaired liver function. Blood dyscrasias are also relatively frequent and a few studies reported changes in serum immunoglobulin concentrations with valproate treatment. We describe a case of panhypogammaglobulinemia with transient pancytopenia due to valproate. Pancytopenia was recovered after discontinuation of valproate but panhypogammaglobulinemia has been persisting. Intravenous immunoglobulin is being administrated monthly. Previous reports describe that other sodium channel blockers, such as phenytoin and carbamazepine, have been associated with hypogammaglobulinemia. This report also suggests that immunodeficiencies can be caused by valproate.

Outcome of Intensive Therapy for Children with Relapsed Acute Myeloid Leukemia: A Single Institution Korean Study.

PURPOSE: Approximately 30%-40% of pediatric acute myeloid leukemia (AML) patients relapse. In this study, we analyzed the outcome and prognostic factors of relapsed AML patients who had previously received first-line therapy at our institution. MATERIALS AND METHODS: The study group consisted of 50 patients who had been diagnosed with AML from April 2009 to December 2018, and then showed first relapse. Thirty-two of the patients (64%) had previously received allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). RESULTS: Forty-five of the patients (90%) received intensive chemotherapy upon diagnosis of relapse, and 76% (34/45) of these patients achieved a second CR. Estimated 5-year overall survival for these 45 patients was 44.9%±7.6%. Time from diagnosis to relapse, extramedullary involvement (EMI) at diagnosis, core binding factor AML, and complex karyotype were significant prognostic factors; in multivariate study, both time from diagnosis to relapse and EMI at diagnosis proved significant. There was no difference in 5-year disease-free survival between patients previously treated with chemotherapy only and those who received HSCT in first CR (52.4%±14.9% vs. 52.6%±11.5%). Of the 19 patients who achieved second CR after previous allogeneic HSCT in first CR and subsequent relapse, 11 were treated with chemotherapy only, and seven survive disease-free. CONCLUSION: Intensive therapy allowed for long-term survival in 40%-50% of patients, and 50% of patients who achieved second CR, regardless of prior treatment modalities in first CR. Intensive treatment may allow for salvage of a significant portion of patients with relapsed pediatric AML.

High Failure-Free Survival after Unrelated Donor Peripheral Blood Stem Cell Transplantation in Pediatric Severe Aplastic Anemia.

The use of alternative donor peripheral blood stem cell transplantation (PBSCT) has increased in recent years. In this study, we analyzed the effect of stem cell source and HLA disparity on outcomes in pediatric patients with severe aplastic anemia (SAA). A total of 134 patients who underwent HSCT with nonmyeloablative conditioning between 2006 and 2020 were enrolled and classified into 3 groups: HLA-matched bone marrow transplantation (M-BMT; n = 24), HLA-matched PBSCT (M-PBSCT; n = 66), and HLA-mismatched PBSCT (MM-PBSCT; n = 44). Significantly higher stem cell doses were obtained for PBSCT than for BMT. A total of 13 patients experienced secondary graft failure (GF), with a cumulative incidence (CI) of 10.0%. HLA-mismatched PBSCT and a very severe degree of disease significantly decreased the incidence of secondary GF. The CI of grade II-IV acute graft-versus-host disease (GVHD) was significantly higher in PBSCT than in BMT, but the CI of grade III-IV acute GVHD and CI of chronic GVHD requiring systemic treatment did not increase in PBSCT. The estimated 5-year overall survival (OS), failure-free survival (FFS), and GVHD-free failure-free survival (GFFS) of the total cohort were 93.0%, 89.5%, and 77.5%, respectively. The most favorable FFS was observed in the MM-PBSCT group (97.6%; P = .03), whereas OS and GFFS were similar across the 3 groups. In multivariate analysis, HLA mismatch and short time from diagnosis to transplantation were associated with superior FFS. Unrelated donor PBSCT with low-intensity SAA conditioning showed favorable outcomes in terms of low rate of secondary GF, higher FFS, and manageable GVHD regardless of HLA compatibility. Our findings suggest the feasibility of PBSCT from unrelated donors, resulting in the possible expansion of the donor pool in transplantation for pediatric SAA. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Prognostic impact of total body irradiation dose in pediatric acute lymphoblastic leukemia patients treated with allogeneic hematopoietic stem cell transplantation in second complete remission.

Background: Allogeneic HSCT may improve survival in pediatric ALL patients who relapse. In this study, we analyzed the outcome and prognostic factors of 62 ALL patients (35 male, 56.5%) who received allogeneic HSCT in second complete remission (CR) at our institution between April 1st 2009 and December 31st 2019. Methods: The median time from diagnosis to relapse was 35.1 months (range, 6.0‒113.6 mo). Fifty-three patients (85.5%) experienced bone marrow relapse only. The number of patients who received transplant according to each donor type was as follows: HLA matched family donor 17 (27.4%), matched unrelated donor (UD) 22 (35.5%), mismatched donor 23 (37.1%). All patients received HSCT with a myeloablative conditioning, 58 patients (93.5%) with the incorporation of TBI [31 patients 12 Gray (Gy), 24 patients 13.2 Gy, 3 patients 8 Gy]. Results: The 5-year event-free survival (EFS), and overall survival of the study group was 41.3±6.3% (26/62), and 42.3±6.6% (27/62), respectively. The cumulative incidence of relapse and transplant-related mortality was 57.1±6.4% and 1.6±1.6%, respectively. Infant ALL, shorter time from diagnosis to relapse, and TBI dose of 12 Gy, rather than 13.2 Gy, resulted in significantly worse EFS. In multivariate analysis, infant ALL and TBI dose of 12 Gy during conditioning predicted significantly lower EFS. Conclusion: In our study group, treatment with a higher dose of TBI during conditioning resulted in better EFS for ALL patients who underwent HSCT in second CR. Further study is needed to determine potential long-term complications associated with a higher TBI dose.

Differing Outcomes of Patients with High Hyperdiploidy and ETV6-RUNX1 Rearrangement in Korean Pediatric Precursor B Cell Acute Lymphoblastic Leukemia.

PURPOSE: Recent cooperative trials in pediatric acute lymphoblastic leukemia (ALL) report long-term event-free survival (EFS) of greater than 80%. In this study, we analyzed the outcome and prognostic factors for patients with precursor B cell ALL (n=405) diagnosed during a 10-year period (2005-2015) at our institution. MATERIALS AND METHODS: All patients were treated with a uniform institutional regimen based on four risk groups, except for steroid type; patients diagnosed up till 2008 receiving dexamethasone, while subsequent patients received prednisolone. None of the patients received cranial irradiation in first complete remission. RESULTS: The 10-year EFS and overall survival was 76.3%±2.3% and 85.1%±1.9%. Ten-year cumulative incidence of relapse, any central nervous system (CNS) relapse and isolated CNS relapse was 20.8%±2.2%, 3.7%±1.1%, and 2.5%±0.9%, respectively. A comparison of established, good prognosis genetic abnormalities showed that patients with high hyperdiploidy had significantly better EFS than those with ETV6-RUNX1 rearrangement (10-year EFS of 91.2%±3.0% vs. 79.5%±4.4%, p=0.033). For the overall cohort, male sex, infant ALL, initial CNS involvement, and Philadelphia chromosome (+) ALL were significant factors for lower EFS in multivariate study, while high hyperdiploidy conferred favorable outcome. For high and very high risk patients (n=231), high hyperdiploidy was the only significant factor for EFS in multivariate study. CONCLUSION: Regarding good prognosis genetic abnormalities, patients with high hyperdiploidy had significantly better outcome than ETV6-RUNX1 (+) patients. High hyperdiploidy was a major, favorable prognostic factor in the overall patient group, as well as the subgroup of patients with higher risk.

Effectiveness and Safety of Clofarabine Monotherapy or Combination Treatment in Relapsed/Refractory Childhood Acute Lymphoblastic Leukemia: A Pragmatic, Non-interventional Study in Korea.

PURPOSE: Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development. MATERIALS AND METHODS: In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed. RESULTS: Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events. CONCLUSION: Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.

Frequency of CD4(+)CD25(hi)FOXP3(+) regulatory T cells has diagnostic and prognostic value as a biomarker for acute graft-versus-host-disease.

The relationship between regulatory T cells (Tregs) and acute graft-versus-host disease (aGVHD) in clinical allogeneic bone marrow transplantation (BMT) recipients is not well established. We conducted a prospective analysis of peripheral blood Tregs as determined by the frequency of CD4(+)CD25(hi)FOXP3(+) lymphocytes in 215 BMT patients. Autologous BMT patients (N = 90) and allogeneic BMT patients without GVHD (N = 65) had similar Treg frequencies, whereas allogeneic patients with GVHD (N = 60) had Treg frequencies that were 40% less than those without GVHD. Treg frequencies decreased linearly with increasing grades of GVHD at onset, and correlated with eventual maximum grade of GVHD (P < .001). In addition, frequency of Tregs at onset of GVHD predicted the response to GVHD treatment (P = .003). Patients with Treg frequencies less than the median had higher nonrelapse mortality (NRM) than patients with Tregs greater than the median, but experienced equivalent relapse mortality, resulting in an inferior survival at 2 years (38% versus 63%, P = .03). Treg frequency may therefore have important prognostic value as a biomarker of aGVHD.

High incidence of RAS pathway mutations among sentinel genetic lesions of Korean pediatric BCR-ABL1-like acute lymphoblastic leukemia.

INTRODUCTION: Recent advances in genetic analysis have led to the discovery of novel genetic subtypes of precursor B-cell acute lymphoblastic leukemia (B-ALL) with prognostic relevance. In this study, we studied a cohort of pediatric B-ALL patients to retrospectively determine the incidence of patients harboring novel genetic subtypes, as well as their outcome. METHODS: B-ALL patients (N = 190) diagnosed in a single Korean hospital were included in the study. Patients' medical records were reviewed for data on established genetic abnormalities and outcome. CRLF2 expression was analyzed by quantitative RT-PCR. Anchored multiplex PCR-based enrichment was used to detect fusions and point mutations in 81 ALL-related genes. RESULTS: Incidence of established recurrent genetic subtypes was as follows: high hyperdiploidy (21.6%), ETV6-RUNX1 (21.6%), BCR-ABL1 (7.9%), KMT2A rearrangement (7.4%) TCF3-PBX1/TCF3-HLF (7.4%), and hypodiploidy (1.1%). Incidence of new genetic subtypes was as follows: BCR-ABL1-like (13.2%), ETV6-RUNX1-like (2.1%), EWSR1-ZNF384 (1.1%), and iAMP21 (1.1%). Median age at diagnosis of BCR-ABL1-like ALL was 6.8 years. According to type of genetic abnormality, BCR-ABL1-like ALL was divided into ABL class (12%), CRLF2 class (8%), JAK-STAT class (12%), and RAS class (68%). The 5-year event-free survival (EFS) of BCR-ABL1-like patients was significantly inferior to non-BCR-ABL1-like low- and standard-risk patients (71.5 ± 9.1% vs 92.5 ± 3.2%, P = .001) and comparable to non-BCR-ABL1-like high (75.2 ± 6.2%) and very high-risk patients (56.8 ± 7.4%). All four ETV6-RUNX1-like patients survived event-free. CONCLUSION: Analogous to previous studies, incidence of BCR-ABL1-like ALL in our cohort was 13.2% with outcome comparable to high and very high-risk patients. A significantly high number of RAS class mutations was a distinct feature of our BCR-ABL1-like ALL group.

Outcome and prognostic factors of children with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib followed by allogeneic hematopoietic cell transplantation in first remission.

BACKGROUND: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a subset of ALL with poor prognosis. Here, we analyzed the outcomes and prognostic factors of children with Ph+ ALL who received imatinib and chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR). METHODS: Thirty-one Ph+ ALL patients (female 10) diagnosed from January 2005 to December 2016 were included in the study. All patients were treated with imatinib and chemotherapy before HCT. Bone marrow (BM) evaluations included real-time quantitative polymerase chain reaction (RQ-PCR) study of the BCR-ABL1 fusion transcript. All patients received HCT with total body irradiation (TBI)-based conditioning at a median of 6.4 (range, 4.2-47.1) months from diagnosis. RESULTS: Compared to values at diagnosis, the median decrement of RQ-PCR value post-consolidation, and prior to HCT was -3.7 Log and -4.8 Log, respectively. The 5-year event-free survival (EFS) and overall survival of the patients were 64.5±9.4% (20/31) and 75.0±8.3% (23/31) respectively. Events included relapse (N=5) and death in CR post-HCT (N=6). The 5-year incidence of molecular relapse was 30.9±9.1% (9/31). An RQ-PCR decrement of at least -4 Log post-consolidation significantly predicted lower incidence of molecular relapse: 7.7±7.7% for ≥-4 Log decrement, 50.0±13.8% for <-4 Log decrement (P=0.027). CONCLUSION: Decrement in RQ-PCR for the BCR-ABL1 transcript that was determined after consolidation was the only significant prognostic factor for incidence of molecular relapse. In the post-induction TKI initiation setting, steadfast imatinib treatment during consolidation may allow for optimum post-HCT outcomes.

Allogeneic hematopoietic stem cell transplantation in congenital hemoglobinopathies with myeloablative conditioning and rabbit anti-thymocyte globulin.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for ß-thalassemia major (TM) and sickle cell disease (SCD) in children. Graft-versus-host disease (GVHD) and treatment-related mortality (TRM) remain significant challenges to improving survival after HSCT. Here, we analyzed the outcome of TM and SCD patients, who received allogeneic HSCT with myeloablative conditioning at our institution. METHODS: Twenty-two patients (15 TM, 7 SCD), with a median age of 9 years (range, 1.6-16.9), underwent allogeneic HSCT using busulfan, cyclophosphamide and rabbit anti-thymocyte globulin-based conditioning. Cells were derived from either the bone marrow (8 patients), or peripheral blood stem cells (14 patients). The majority of patients received HSCT from a matched sibling donor (N=18). GVHD prophylaxis included cyclosporine and short course methotrexate. RESULTS: All patients achieved donor engraftment. Two SCD patients died from TRM-related grade IV gut GVHD (N=1) or severe bronchiolitis obliterans (BO) (N=1). Cumulative incidence of acute and chronic GVHD was 36.4% and 32.7%, respectively. Veno-occlusive disease (VOD) occurred in 8 patients (36.4%), but resolved in all instances. Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative disease (PTLD) occurred in 1 patient. The overall survival (OS) was 90.9% (TM 100%, SCD 71.4%), with all patients achieving transfusion independence, while 8 achieved complete donor chimerism. CONCLUSION: Busulfan, cyclophosphamide, and ATG-based conditioning for HSCT of TM and SCD patients did not result in graft failure, although modifications may be required to reduce VOD incidence. Further changes to donor type and cell source prioritization are necessary to minimize TRM and morbidity caused by GVHD.

Treatment and response of autoimmune cytopenia occurring after allogeneic hematopoietic cell transplantation in children.

BACKGROUND: Autoimmune cytopenia (AIC) is a rare complication of allogeneic hematopoietic cell transplantation (HCT). In this study, we reviewed the diagnosis, treatment and response to therapy for pediatric patients with post-HCT AIC at our institution. METHODS: Of the 292 allogeneic HCTs performed from January, 2011 to December, 2015 at the Department of Pediatrics, The Catholic University of Korea, seven were complicated by post-HCT AIC, resulting in an incidence of 2.4%. RESULTS: All seven patients with post-HCT AIC had received unrelated donor transplant. Six of seven patients had a major donor-recipient blood type mismatch. The subtypes of AIC were as follows: immune thrombocytopenia (ITP) 2, autoimmune hemolytic anemia (AIHA) 2, Evans syndrome 3. Median time from HCT to AIC diagnosis was 3.6 months. All but one patient responded to first line therapy of steroid±intravenous immunoglobulin (IVIG), but none achieved complete response (CR) with this treatment. After a median duration of treatment of 15.3 months, two patients with ITP achieved CR and five had partial response (PR) of AIC. Five patients were treated with rituximab, resulting in the following response: 2 CR, 2 PR, 1 no response (NR). Median time to response to rituximab was 26 days from first infusion. All patients are alive without event. CONCLUSION: Post-HCT AIC is a rare complication that may not resolve despite prolonged therapy. Rapid initiation of second line agents including but not limited to B cell depleting treatment should be considered for those that fail to achieve CR with first line therapy.

Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute Lymphoblastic Leukemia Treated at a Single Institution in Korea.

PURPOSE: ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables. MATERIALS AND METHODS: Sixty-three patients were diagnosed with ETV6/RUNX1 (+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of additional cytogenetic abnormalities. RESULTS: The 5-year event-free survival was 84.1±4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9±4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5±6.9%. CONCLUSION: ETV6/RUNX1 (+) ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end ofremission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.

A Novel Syntaxin 11 Gene (STX11) Mutation c.650T>C, p.Leu217Pro, in a Korean Child With Familial Hemophagocytic Lymphohistiocytosis.

We report the first Far Eastern case of a Korean child with familial hemophagocytic lymphohistiocytosis (HLH) caused by a novel syntaxin 11 (STX11) mutation. A 33-month-old boy born to non-consanguineous Korean parents was admitted for intermittent fever lasting one week, pancytopenia, hepatosplenomegaly, and HLH in the bone marrow. Under the impression of HLH, genetic study revealed a novel homozygous missense mutation of STX11: c.650T>C, p.Leu217Pro. Although no large deletion or allele drop was identified, genotype analysis demonstrated that the homozygous c.650T>C may have resulted from the duplication of a maternal (unimaternal) chromosomal region and concurrent loss of the other paternal allele, likely caused by meiotic errors such as two crossover events. A cumulative study of such novel mutations and their effects on specific protein interactions may deepen the understanding of how abnormal STX1 expression results in deficient cytotoxic function.