Improved Outcome of a Reduced Toxicity-Fludarabine, Cyclophosphamide, plus Antithymocyte Globulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia: Comparison of 2 Multicenter Prospective Studies.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for severe aplastic anemia (SAA); however, the optimal conditioning regimen for HSCT with an unrelated donor has not yet been defined. A previous study using a fludarabine (FLU), cyclophosphamide (Cy), and antithymocyte globulin (ATG) conditioning regimen (study A: 50 mg/kg Cy once daily i.v. on days -9, -8, -7, and -6; 30 mg/m(2) FLU once daily i.v. on days -5, -4, -3, and -2; and 2.5 mg/kg of ATG once daily i.v. on days -3, -2, and -1) demonstrated successful engraftment (100%) but had a high treatment-related mortality rate (32.1%). Therefore, given that Cy is more toxic than FLU, we performed a new phase II prospective study with a reduced-toxicity regimen (study B: 60 mg/kg Cy once daily i.v. on days -8 and -7; 40 mg/m(2) FLU once daily i.v. on days -6, -5, -4, -3, and -2; and 2.5 mg/kg ATG once daily i.v. on 3 days). Fifty-seven patients were enrolled in studies A (n = 28) and B (n = 29), and donor type hematologic recovery was achieved in all patients in both studies. The overall survival (OS) and event-free survival (EFS) rates of patients in study B was markedly improved compared with those in study A (OS: 96.7% versus 67.9%, respectively, P = .004; EFS: 93.3% versus 64.3%, respectively, P = .008). These data show that a reduced-toxicity conditioning regimen with FLU, Cy, and ATG may be an optimal regimen for SAA patients receiving unrelated donor HSCT.

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.

Varicella with rapidly progressive hepatitis presenting with multiple hepatic nodules in a child with acute leukemia.

Abdominal pain may precede the characteristic varicella skin lesions in immunocompromised patients with visceral varicella. The absence of skin lesions may delay timely diagnosis and treatment of varicella for those patients. Furthermore, abdominal imaging findings to provide information to diagnose visceral varicella have rarely been reported. Varicella was diagnosed in a 5-year-old boy with acute lymphoblastic leukemia complaining of fever and abdominal pain followed by papulovesicular skin lesions. Later, the patient was found to have rapidly progressive acute hepatitis, and abdominal computed tomography showed multiple hypodense hepatic nodules. The patient was treated with intravenous acyclovir, intravenous immunoglobulin, and empirical antibiotic and antifungal therapy. However, his fever and abdominal pain persisted, and a laparoscopic liver biopsy was performed to differentiate other causes of the persisting symptoms. Eventually, the patient was diagnosed with visceral varicella based on histopathologic findings. In conclusion, visceral varicella should be considered in immunocompromised patients with abdominal pain and multiple hypodense hepatic nodules on abdominal imaging studies. However, bacteria, fungi, and tuberculosis can produce similar imaging findings; therefore, a biopsy may be necessary in patients not responding to antiviral therapy.

Cytomegalovirus infection in seropositive unrelated cord blood recipients: a study of 349 Korean patients.

To gain insight into the natural history of cytomegalovirus (CMV) infection following unrelated cord blood transplantation (UCBT) in seropositive patients, we analyzed the data of 349 seropositive patients who received UCBT in Korea between 2000 and 2011. CMV reactivation occurred in 49 % (171/349) of the CMV-seropositive transplant recipients at a median of 31 days post UCBT. One hundred sixty-four out of 171 patients (96 %) received preemptive therapy. The median duration of CMV reactivation was 29 days. In multivariate analysis, weight >22 kg, use of total body irradiation, use of pre-transplant antithymocyte globulin, graft-versus-host disease (GVHD) prophylaxis with mycophenolate mofetil, and presence of grade II-IV acute GVHD were independent predictors of CMV reactivation. CMV reactivation did not impact transplantation-related mortality (TRM), leukemia relapse, or survival. CMV disease was diagnosed in 62 patients (17.8 %) at a median 55 days after UCBT. Longer duration of CMV reactivation was the only risk factor for progression to CMV disease (p = 0.01). CMV disease resulted in higher TRM (56.0 vs. 31.4 %, p < 0.01) and lower survival (36.1 vs. 55.1 %, p = 0.02).

Serum galactomannan index for early prediction of mortality in immunocompromised children with invasive pulmonary aspergillosis.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is the most common invasive fungal disease in immunocompromised patients, and it has a 30 % mortality rate despite appropriate antifungal therapy. This retrospective study was performed to determine risk factors for mortality in immunocompromised children with IPA. METHODS: Medical records of 45 probable/proven IPA cases diagnosed in children with hematologic/oncologic diseases were reviewed. Selected cases were divided into the survival (n = 30) and fatality (n = 15) groups based on survival at 12 weeks after antifungal therapy. Clinical characteristics and serum galactomannan indices (GMIs) were compared between the two groups. RESULTS: Significantly more children in the fatality group were male (p = 0.044), not in complete remission of the underlying malignancies (p = 0.016), and had received re-induction/salvage or palliative chemotherapy (p = 0.035) than those in the survival group. However, none of these factors was significantly associated with mortality in a multivariate analysis. Serum GMIs were higher in the fatality group than in the survival group during the entire period of antifungal therapy, and serum GMI at 1 week after antifungal therapy was most significantly associated with mortality. A serum GMI > 1.50 at 1 week after antifungal therapy exhibited a sensitivity and specificity of 61.5 % and 89.3 %, respectively, in predicting mortality within 12 weeks after antifungal therapy. CONCLUSIONS: Higher serum GMI in the early phase of antifungal therapy was associated with mortality in immunocompromised children with IPA. These children should receive more intensive care for IPA than others.

Cytomegalovirus retinitis diagnosed after completion of chemotherapy for acute lymphoblastic leukemia in an adolescent.

Although cytomegalovirus (CMV) retinitis is usually diagnosed in allogeneic hematopoietic cell transplantation recipients among patients with hematologic and oncologic disease, it can also occur in acute leukemia patients who have not received hematopoietic cell transplantation. However, CMV retinitis diagnosed after completion of chemotherapy for acute leukemia has not previously been reported. A 17-year-old boy was diagnosed with CMV retinitis 3 months after completion of chemotherapy for acute lymphoblastic leukemia, and his retinitis was assumed to be caused by a delayed immune reconstitution after chemotherapy. The patient was treated with intravenous and intravitreous ganciclovir therapy, and subsequently underwent surgery for retinal detachment.

Clinical Features and Prognosis of Invasive Pulmonary Aspergillosis in Korean Children with Hematologic/Oncologic Diseases.

Invasive pulmonary aspergillosis (IPA) is the most frequent form of invasive fungal diseases in immunocompromised patients. However, there are only a few studies on IPA in immunocompromised children in Korea. This study was designed to characterize IPA in Korean children with hematologic/oncologic diseases. Medical records of children with hematologic/oncologic diseases receiving antifungal therapy were reviewed. The enrolled children were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. During the study period, 265 courses of antifungal therapy were administered to 166 children. Among them, two (0.8%) episodes of proven IPA, 35 (13.2%) of probable IPA, and 52 (19.6%) of possible IPA were diagnosed. More children in the IPA group suffered from neutropenia lasting for more than two weeks (51.4% vs. 21.9%, P<0.001) and showed halo signs on the chest computed tomography (78.4% vs. 40.7%, P<0.001) than in the non-IPA group. No other clinical factors showed significant differences between the two groups. Amphotericin B deoxycholate was administered as a first line antifungal agent in 33 (89.2%) IPA group episodes, and eventually voriconazole was administered in 27 (73.0%) episodes. Ten (27.0%) children in the IPA group died within 12 weeks of antifungal therapy. In conclusion, early use of chest computed tomography to identify halo signs in immunocompromised children who are expected to have prolonged neutropenia can be helpful for early diagnosis of IPA and improving prognosis of children with IPA.

Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children.

Some prospective studies showed that rabbit antithymocyte globulin was inferior to horse antithymocyte globulin as first-line therapy for patients with severe aplastic anemia. We retrospectively analyzed the clinical outcome of 455 children with severe aplastic anemia who received horse antithymocyte globulin (n=297) or rabbit antithymocyte globulin (n=158) combined with cyclosporine as first-line therapy between 1992 and 2010. The response rates were comparable between the horse and rabbit antithymocyte globulin groups at 3 months [46% (136/294) versus 42% (66/153), P=0.55] and 6 months [60% (178/292) versus 55% (87/143), P=1.0]. Using multivariate analysis, differences in antithymocyte globulin preparations were not associated with response rates. However, 2-year and 10-year overall survival rates in the horse antithymocyte globulin group were significantly better than those in the rabbit antithymocyte globulin group (2-year overall survival: 96% versus 87%, 10-year overall survival: 92% versus 84%, P=0.004). On the basis of multivariate analysis, use of rabbit antithymocyte globulin was a significant adverse factor for overall survival (hazard ratio = 3.56, 95% confidence interval, 1.53 - 8.28, P=0.003). Rabbit antithymocyte globulin caused more profound immunosuppression, which might be responsible for the higher incidence of severe infections. Considering that there are no studies showing the superiority of rabbit antithymocyte globulin over horse antithymocyte globulin, horse antithymocyte globulin should be recommended as a first-line therapy. However, our results justify the use of rabbit antithymocyte globulin as first-line therapy if horse antithymocyte globulin is not available.

Unrelated donor cord blood transplantation for non-malignant disorders in children and adolescents.

This study analyzes the data reported to the Korean Cord Blood Registry between 1994 and 2008, involving children and adolescents with non-malignant diseases. Sixty-five patients were evaluated in this study: SAA (n = 24), iBMFS, (n = 16), and primary immune deficiency/inherited metabolic disorder (n = 25). The CI of neutrophil recovery was 73.3% on day 42. By day 100, the CI of acute grade II-IV graft-versus-host disease was 32.3%. At a median follow-up of 71 months, five-yr OS was 50.7%. The survival rate (37.5%) and CI of neutrophil engraftment (37.5%) were lowest in patients with iBMFS. Deaths were mainly due to infection, pulmonary complications, and hemorrhage. In a multivariate analysis, the presence of >3.91 × 10(5) /kg of infused CD34 + cells was the only factor consistently identified as significantly associated with neutrophil engraftment (p = 0.04) and OS (p = 0.03). UCBT using optimal cell doses appears to be a feasible therapy for non-malignant diseases in children and adolescents for whom there is no appropriate HLA-matched related donor. Strategies to reduce transplant-related toxicities would improve the outcomes of UCBT in non-malignant diseases.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.

Pre-engraftment syndrome after unrelated cord blood transplantation: a predictor of engraftment and acute graft-versus-host disease.

Pre-engraftment syndrome (PES) is poorly characterized, and its clinical significance and the prognostic impact after unrelated cord blood transplantation (CBT) are unclear. To address these issues, we retrospectively analyzed the incidence, risk factors, and clinical outcomes of PES in unrelated CBT recipients. Data of 381 patients who received unrelated CBT from 18 medical centers in Korea were reviewed. PES was defined as unexplained fever >38.3°C not associated with infection, and/or unexplained skin rash with or without evidence of fluid retention before neutrophil recovery. PES developed in 102 patients (26.8%) at a median of 7 days after CBT. Of these patients, 74 patients (72.5%) received intravenous corticosteroid at a median dose of 1 mg/kg/day, and of these, 95% showed clinical improvement. Risk factors for developing PES included low risk disease, myeloablative conditioning, graft-versus-host disease (GVHD) prophylaxis without methotrexate or corticosteroid, and >5.43 x 10(7)/kg infused nucleated cells. Absence of PES was one of the risk factors for graft failure in multivariate analysis. The cumulative incidence of grade II to grade IV acute GVHD by 100 days after CBT was higher in patients with PES than in those without PES (56.0% versus 34.4%, P < .01). PES was not associated with chronic GVHD, treatment-related mortality, relapse, or overall survival. PES seems to be common after CBT and may be associated with enhanced engraftment without significant morbidity.

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.

Clinical characteristics and antimicrobial susceptibilities of viridans streptococcal bacteremia during febrile neutropenia in patients with hematologic malignancies: a comparison between adults and children.

BACKGROUND: This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies. METHODS: The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively. A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB. RESULTS: A total of 202 episodes (141 in adults, 61 in children) of VSB were identified. Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB. For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%). Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004). The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children. Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002). However, in multivariate analysis, cefepime susceptibility had no impact on clinical outcome. CONCLUSIONS: There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility. Hence, different antibiotic treatment strategies may not be necessary.

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.

Factors related to decreased bone mineral density in childhood cancer survivors.

The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and to identify factors related to the decreased BMD in childhood cancer survivors. We studied 78 patients (34 boys, 44 girls) treated for childhood cancer. Twenty (25.7%) patients had lumbar BMD (LBMD) standard deviation score (SDS) lower than -2. Nineteen (24.4%) patients had femur neck BMD (FNBMD) SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17 ± 1.39 vs -0.43 ± 1.33, P = 0.025). The risk of having LBMD SDS < -2 was higher in the patients treated with glucocorticoid (GC) for graft-versus-host disease (GVHD) (36.6% vs 13.5%; odds ratio [OR], 3.7; P = 0.020). In multivariate logistic regression analysis, longer duration of GC treatment for GVHD (OR, 1.12; 95% confidence interval [CI], 1.05-1.20) and lower body mass index (BMI) SDS (OR, 0.59; 95% CI, 0.36-0.95) were associated with decreased LBMD SDS. These findings suggest that prolonged GC use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.

Life-threatening scrub typhus with hemophagocytosis and acute respiratory distress syndrome in an infant.

Scrub typhus is a rickettsial disease, caused by Orientia tsutsugamushi, which is transmitted via the bite of a chigger. This disease is one of the most important infectious diseases in the Asia-Pacific area; however, a severe infant case has not yet been reported. Here, we present the case of an 8-month-old boy with scrub typhus accompanied by hemophagocytic lymphohistiocytosis (HLH). His rapid course was complicated by acute respiratory distress syndrome (ARDS), status epilepticus and disseminated intravascular coagulation (DIC). He recovered after clarithromycin therapy and intensive supportive care. Although being extremely rare, scrub typhus can be life-threatening in an infant; therefore, physicians in endemic countries should be aware of the necessity for early recognition and prompt treatment of suspected cases.

Assessment of serologic immunity to diphtheria-tetanus-pertussis after treatment of Korean pediatric hematology and oncology patients.

The aim of this study was to investigate the diphtheria-tetanus-pertussis antibody titers after antineoplastic treatment and to suggest an appropriate vaccination approach for pediatric hemato-oncologic patients. A total of 146 children with either malignancy in remission after cessation of therapy or bone marrow failure were recruited. All children had received routine immunization including diphtheria-tetanus-acellular pertussis vaccination before diagnosis of cancer. The serologic immunity to diphtheria, tetanus and pertussis was classified as: completely protective, partially protective, or non-protective. Non-protective serum antibody titer for diphtheria, tetanus and pertussis was detected in 6.2%, 11.6%, and 62.3% of patients, respectively, and partial protective serum antibody titer for diphtheria, tetanus and pertussis was seen in 37%, 28.1%, and 8.9% of patients. There was no significant correlation between the severity of immune defect and age, gender or underlying disease. Revaccination after antineoplastic therapy showed significantly higher levels of antibody for each vaccine antigen. Our data indicates that a large proportion of children lacked protective serum concentrations of antibodies against diphtheria, tetanus, and pertussis. This suggests that reimmunization of these patients is necessary after completion of antineoplastic treatment. Also, prospective studies should be undertaken with the aim of devising a common strategy of revaccination.

Current status of pediatric umbilical cord blood transplantation in Korea: a multicenter retrospective analysis of 236 cases.

We report the outcome of 236 pediatric umbilical cord blood transplantations (UCBT) performed in Korea. Given that the sources of the grafts were mostly unrelated donors (n = 226; 95.8%), only the results of unrelated UCBT were included for all statistics. The most frequent primary disease was acute leukemia (n = 167). In total, 91.7% of recipients were seropositive for cytomegalovirus (CMV). The median doses of nucleated cells and CD34+ cells were 4.84 × 10(7)/kg and 2.00 × 10(5)/kg, respectively. The median times to neutrophil (>0.5 × 10(9)/L) and platelet recovery (>20 × 10(9)/L) were 18 and 45 days, respectively. Grade 2-4 acute graft-versus-host-disease (GVHD) and chronic GVHD developed in 41.1 and 36.1% of cases, respectively. Forty-five patients developed CMV disease. The 5-year overall and event-free survival were 47.5 and 36.9%, respectively. Multivariate analysis revealed that adverse factors for survival of the whole cohort were total body irradiation-based conditioning (P = 0.007), salvage transplant (P = 0.001), failure to achieve early complete chimerism (P < 0.0005), and CMV disease (P = 0.001). The outcomes of the single- and double-unit UCBT (n = 64) were similar, while double-unit recipients were heavier (P < 0.0005) and older (P < 0.0005). We conclude that double-unit UCBT is a reasonable option for older or heavier children and that the thorough surveillance of CMV infection and the development of an effective CMV therapeutic strategy may be especially important for Korean children, whose CMV seroprevalence exceeds 90%.

Epidemiology and clinical long-term outcome of childhood aplastic anemia in Korea for 15 years: retrospective study of the Korean Society of Pediatric Hematology Oncology (KSPHO).

PURPOSE: Aplastic anemia (AA) is a rare hematologic disease characterized by pancytopenia and hypocellular marrow. The Korean Society of Pediatric Hematology Oncology investigated retrospectively the incidence, survival, and transfusion independency according to treatment strategies in AA. METHODS: All the questionnaires were sent to members for medical records. We collected and analyzed 702 available data. RESULTS: The male and female ratio was 1.2, and the median age at diagnosis was 9.3 years. The annual incidence of Korean children with AA was 5.16 per million per year. Constitutional anemia was diagnosed in 44 children. In acquired AA, causes were identified in 39 children. Severe AA (SAA) at initial diagnosis was more common than nonsevere AA. The overall survival was 47.8% with supportive care, 68.1% with immunosuppressive therapy (IST), and 81.8% with hematopoietic stem cell transplantation. In IST, response rate was 65.7%, and relapse rate after response was 54.4% within a median of 23.0 months. The factors with overall survival were severity of disease in supportive care, severity and response in IST, donor type, graft failure, and posttransplant events in hematopoietic stem cell transplantation. CONCLUSIONS: Long-term outcome in AA was dependent on treatment strategies. These Korean results may help research and prospective international clinical trials for childhood AA.

Primary ovarian dysfunction after hematopoietic stem cell transplantation during childhood: busulfan-based conditioning is a major concern.

We evaluated the incidence of patient/treatment factors associated with primary ovarian failure (POF) after hematopoietic stem cell transplantation (HSCT) during childhood. Fifty girls over 12 years of age (15.0 +/- 2.2) who were referred to the pediatric endocrinology clinic between March 2002 and March 2010 after HSCT at the Catholic HSCT center were enrolled in the study. In total, 36 (72%) out of 50 patients developed POF. Twenty-three patients were diagnosed and treated as chronic graft-versus-host disease. As preparative regimens for HSCT, 23 patients received total body irradiation (TBI)-based regimen, 19 received busulfan (BU)-based regimen, 4 received both BU- and TBI-based, and 4 received reduced intensity conditioning regimen. In a univariate logistic regression analysis, the BU-based regimen (p = 0.028) showed a strong relationship with POF. The incidence of POF according to the route of BU administration, between orally and intravenously, were not different (p = 0.435). These results emphasize the importance of monitoring these patients at regular intervals and the need to develop complementary HSCT protocols for preventing POF in children.