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ABSTRACT: 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.
Pediatric Transplantation 04/2013; · 1.48 Impact Factor
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ABSTRACT: Numerous studies have shown the antiproliferative effect of iron chelating agents (ICA), which have been traditionally used in patients with secondary iron overload (SIO). Because the in vivo model for these studies has been animals with normal iron status, the antileukemic effect of ICAs in the SIO condition has not been clearly determined. We investigated the in vitro and in vivo effects of ICAs in murine leukemic cell lines with respect to the iron status. The viability of both EL4 cells and L1210 cells incubated with either deferoxamine (DFO) or deferasirox (DFX) decreased in a concentration-dependent manner. This effect was most prominent in L1210 cells treated with DFX. The viability of L1210 cells incubated with both ICAs did not change regardless of the presence of ferric chloride. The percentage of apoptosis in L1210 cells treated with DFO or DFX increased in a concentration-dependent manner; however, the expression of Fas showed no significant change. The non-SIO mice and SIO mice bearing L1210 cells showed longer survival than other groups when treated with DFX, whereas the SIO mice treated with DFO showed shorter survival than the control group. The tumor was significantly smaller in the SIO mice treated with DFX or DFO compared to the control group. The iron content of the liver or the tumor in SIO mice decreased after ICA treatment. This study indicates an antileukemic effect of DFX regardless of iron status and suggests that the use of DFX has a survival benefit for SIO leukemia murine model in terms of iron chelation and antileukemic therapy.
Experimental hematology 02/2013; · 3.11 Impact Factor
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Meerim Park,
Soo Hyun Lee,
Young Ho Lee,
Keon Hee Yoo,
Ki Woong Sung,
Hong Hoe Koo,
Hyoung Jin Kang,
Kyung Duk Park,
Hee Young Shin,
Hyo Seop Ahn, [......],
Hoon Kook,
Tai Ju Hwang,
Eun Kyung Lee,
Jeong Ok Hah,
Yeon Jung Lim,
Hyun Joo Jung,
Jun Eun Park,
Moon Ju Jang,
So Young Chong,
Doyeun Oh
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ABSTRACT: 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 analyzed retrospectively 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 1mg/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-IV acute GVHD by 100 days after CBT was higher in patients with PES than in those without PES (56.0% vs. 34.4%, P<0.01). 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.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2013; · 3.15 Impact Factor
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ABSTRACT: Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT). Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's post-transplant immune reconstitution, and therefore require investigation.
The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK) cell recovery. The impact of pre- and post-transplant variables, including diagnosis of Epstein-Barr virus (EBV) DNAemia posttransplant, on lymphocyte recovery was evaluated.
THE LYMPHOCYTE SUBSETS RECOVERED IN THE FOLLOWING ORDER: NK cells, cytotoxic T cells, B cells, and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16(+)/56(+) cell recovery. Younger patients showed delayed recovery of both CD3(+)/CD8(+) and CD19(+) cells. EBV DNAemia had a deleterious impact on the recovery of both CD3(+) and CD3(+)/CD4(+) lymphocytes at 1 year post-transplant.
In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.
Korean Journal of Pediatrics 01/2013; 56(1):26-31.
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ABSTRACT: A retrospective chart review was performed on 19 patients aged <18 years who developed posterior reversible encephalopathy syndrome as a complication during treatment of acute childhood leukemia. Posterior reversible encephalopathy syndrome was most often observed during acute lymphoblastic leukemia induction chemotherapy (n = 9, 47.4%) and after hematopoietic stem cell transplantation (n = 8, 42.1%). Among eight patients with the complication of posterior reversible encephalopathy syndrome after hematopoietic stem cell transplantation, five (62.5%) had a history of hypertension. In contrast, among 11 patients with the complication of posterior reversible encephalopathy syndrome without hematopoietic stem cell transplantation, only one (9.1%) had a history of hypertension. Moreover, unlike other leukemia induction chemotherapy, posterior reversible encephalopathy syndrome developed only in patients who received acute lymphoblastic leukemia induction chemotherapy. Posterior reversible encephalopathy syndrome patients required long-term anticonvulsant therapy (n = 9, 50.0%) and manifested intractable seizures (n = 3, 16.7%). Sequelae were evident in long-term follow-up magnetic resonance images (n = 5, 26.3%). Acute lymphoblastic leukemia chemotherapy regimens apparently comprised the main predisposing factors for posterior reversible encephalopathy syndrome complicated during induction chemotherapy, compared with hypertension and immunosuppressive agents after hematopoietic stem cell transplantation.
Pediatric Neurology 12/2012; 47(6):436-42. · 1.52 Impact Factor
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ABSTRACT: 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.
British Journal of Haematology 10/2012; · 4.94 Impact Factor
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ABSTRACT: Acute appendicitis has been reported to be relatively rare in pediatric leukemia patients but there is no official data for this in Korea. And there is no consensus for its treatment in this population.
We conducted a retrospective study of 7 patients diagnosed with appendicitis among 1209 pediatric patients who were diagnosed with leukemia from 1996 to 2008 at a single institution in Korea.
The median age at the time of the diagnosis of appendicitis was 12 years (range: 3-15 years), and 3 of the patients were male. The median absolute neutrophil count (ANC) at the time of diagnosis was 0.99×10⁹/L (range: 0-3×10⁹/L). The mean time from the onset of symptoms to the diagnosis was 4 days. All 7 leukemia patients with appendicitis underwent surgery and they demonstrated a survival of 100% without significant complications.
The incidence of appendicitis in pediatric leukemia patients was 0.57% in our study. Early diagnosis with abdominal ultrasound or computed tomography and early surgical resection in leukemic patient with acute appendicitis may be a safer and more effective treatment option. Even when perforation has already occurred and when the patient has an ANC of 0×10⁹/L, surgical treatment may improve overall survival without incurring significant complications.
Yonsei medical journal 07/2012; 53(4):781-7. · 0.77 Impact Factor
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ABSTRACT: 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.
Journal of Tropical Pediatrics 06/2012; · 1.39 Impact Factor
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Soon-Ki Kim,
Hyo-Seop Ahn,
Hee-Jo Back, Bin Cho,
Eun-Jin Choi,
Nak-Gyun Chung,
Pyoung-Han Hwang,
Dae-Chul Jeoung,
Hyung-Jin Kang,
Hyery Kim, [......],
Young-Tak Lim,
Chuhl-Joo Lyu,
Jun-Eun Park,
Kyung-Duk Park,
Sang-Kyu Park,
Kyung-Ha Ryu,
Jong-Jin Seo,
Hee-Young Shin,
Ki-Woong Sung,
Eun Sun Yoo
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ABSTRACT: Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years.
The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study.
The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1±1.9 g/dL, mean corpuscular volume was 93.4±11.6 fL, and mean number of reticulocytes was 19,700/mm(3). The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%).
The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.
The Korean journal of hematology 06/2012; 47(2):131-5.
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ABSTRACT: Improved survival of patients with childhood acute lymphoblastic leukemia (ALL) has drawn attention to the potential for late consequences of previous treatments among survivors, including metabolic syndrome. In this study, we evaluated changes in 3 parameters, namely, random blood glucose, body mass index (BMI), and Z score for BMI (Z-BMI), in children with ALL during chemotherapy and after completion of treatment.
Patients newly diagnosed with ALL from January, 2005 to December, 2008 at Saint Mary's Hospital, The Catholic University of Korea, who completed treatment with chemotherapy only were included (n=107). Random glucose, BMI, and Z-BMI were recorded at 5 intervals: at diagnosis, before maintenance treatment, at completion of maintenance treatment, and 6 and 12 months after completion of maintenance treatment. Similar analyses were conducted on 2 subcohorts based on ALL risk groups.
For random glucose, a paired comparison showed significantly lower levels at 12 months post-treatment compared to those at initial diagnosis (P<0.001) and before maintenance (P<0.001). The Z-BMI score was significantly higher before maintenance than at diagnosis (P<0.001), but decreased significantly at the end of treatment (P<0.001) and remained low at 6 months (P<0.001) and 12 months (P<0.001) post-treatment. Similar results were obtained upon analysis of risk group-based subcohorts.
For a cohort of ALL patients treated without allogeneic transplantation or cranial irradiation, decrease in random glucose and Z-BMI after completion of chemotherapy does not indicate future glucose intolerance or obesity.
Korean Journal of Pediatrics 04/2012; 55(4):121-7.
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ABSTRACT: The survival rate for childhood acute lymphoblastic leukemia (ALL) has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR).
Fifty-three ALL patients (42 men, 79%) who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%). Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD), relapse, 1-year transplant-related mortality (TRM), disease-free survival (DFS), and overall survival (OS).
Cumulative incidences of acute GVHD (grade 2 or above) and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2±6.8% and 48.3±7%, respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010). The rates of relapse and 1 year TRM were 28.9±6.4% and 26.4±6.1%, respectively, and unrelated donor HSCT (P=0.002) and HLA mismatch (P=0.022) were significantly correlated with increased TRM in univariate analysis.
In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.
Korean Journal of Pediatrics 03/2012; 55(3):100-6.
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ABSTRACT: 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.
Journal of Korean medical science 01/2012; 27(1):78-83. · 0.84 Impact Factor
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ABSTRACT: We recently experienced the case of an intramuscular chloroma with infection in a 7-year-old boy diagnosed with acute myeloid leukemia. Conventional magnetic resonance imaging (MRI) showed that the lesion mimicked an abscess, but diffusion-weighted imaging showed no diffusion restriction. These results suggested that the interior cystic portion was serous. On histopathological findings, a chloroma was diagnosed on the wall of a mass. Culture of the interior fluid revealed that Klebsiella pneumoniae was present. MRI differentiation is difficult even with diffusion-weighted images.
Japanese journal of radiology 12/2011; 29(10):735-8. · 0.65 Impact Factor
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Pediatric Hematology and Oncology 11/2011; 28(8):718-20. · 0.89 Impact Factor
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Hyung-Doo Park,
Soo Hyun Lee,
Ki Woong Sung,
Hong Hoe Koo,
Nak Gyun Jung, Bin Cho,
Hak Ki Kim,
In-Ae Park,
Ki-O Lee,
Chang-Seok Ki,
Sun-Hee Kim,
Keon Hee Yoo,
Hee-Jin Kim
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ABSTRACT: Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in children. Hyperactivation of the Ras pathway from gene mutations is known to be the key culprit in the development of JMML. In this study, we investigated Ras pathway mutations and prognostic implication in Korean patients with JMML. A total of 22 Korean patients with JMML were recruited from two institutions (19 boys and three girls; median age, 17 months; range, 1-74 months). Hematologic and cytogenetic findings were reviewed. Mutation analyses involved PTPN11, KRAS, NRAS, and CBL genes by direct sequencing analyses (selected exons except in CBL). Survival analysis was performed by the Kaplan-Meier method. Cytogenetic and/or gene mutations were detected in 18 patients out of 22 (82%). Four patients (18%) had chromosomal abnormalities, with monosomy 7 being the most common. Seventeen (77%) had gene mutations. PTPN11 mutations were detected in 13 patients (59%). The patient heterozygous for c.854T>C had Noonan syndrome. NRAS and KRAS mutations were detected in two patients (9%) and one patient (5%), respectively. A homozygous CBL mutation was detected in one patient (5%; c.1228-2A>G). All mutations detected were previously reported mutations. Survival analyses suggested an unfavorable prognostic implication of PTPN11 mutation, albeit without a statistical significance. Collectively, the results from molecular genetics study and survival analyses suggested a relatively higher frequency and unfavorable prognostic implication of PTPN11 mutations in Korean patients with JMML.
Annals of Hematology 09/2011; 91(4):511-7. · 2.62 Impact Factor
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ABSTRACT: In this study, we analyzed a cohort of children with chronic graft-versus-host disease (GvHD) according to the NIH consensus classification (NCC) in order to observe whether global assessment at diagnosis correlates with GvHD-specific endpoints. We then studied the clinical course of these patients, specifically with regards to episodes of GvHD exacerbation requiring treatment escalation.
Recipients of either allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) from January 2006 to August 2008 at the Department of Pediatrics, The Catholic University of Korea were evaluated for chronic GvHD, which was diagnosed according to the NCC. The course of chronic GvHD in these patients was then followed.
Of 59 evaluable patients, 23 developed chronic GvHD for a cumulative incidence of 39.3%. Upon multivariate analysis, previous acute GvHD (≥grade II) had a significant impact on chronic GvHD incidence. With a median duration of systemic treatment for chronic GvHD of 501 days, no significant relationship was found between initial global severity of chronic GvHD and either duration of immunosuppressive treatment or final clinical response to treatment. Fifteen patients (65%) experienced at least one episode of chronic GvHD exacerbation during the period of follow-up, with a median of four exacerbations in the subgroup of patients who experienced such events. Lung GvHD resulted in the highest number of exacerbations per diagnosed patient, followed by oral GvHD.
Analysis of this small cohort indicates that global assessment as proposed by the NCC may have limited correlations with GvHD-specific endpoints, possibly due to the favorable response of children to treatment.
Yonsei medical journal 09/2011; 52(5):779-86. · 0.77 Impact Factor
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Bin Cho
The Korean journal of hematology 06/2011; 46(2):60-1.
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Dae Chul Jeong,
Nack Gyun Chung,
Hyoung Jin Kang,
Hong Hoe Koo,
Hoon Kook,
Soon Ki Kim,
Sun Young Kim,
Heung Sik Kim,
Hwang Min Kim,
Kyung Duk Park, [......],
Soon Yong Lee,
Young Ho Lee,
Young Tak Lim,
Yeon Jung Lim,
Hye Lim Jung, Bin Cho,
Yong Mook Choi,
Jeong Ok Hah,
Tai Ju Hwang,
Hack Ki Kim
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ABSTRACT: 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.
All the questionnaires were sent to members for medical records. We collected and analyzed 702 available data.
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.
Long-term outcome in AA was dependent on treatment strategies. These Korean results may help research and prospective international clinical trials for childhood AA.
Journal of Pediatric Hematology/Oncology 02/2011; 33(3):172-8. · 1.16 Impact Factor
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ABSTRACT: 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.
Journal of pediatric endocrinology & metabolism: JPEM 01/2011; 24(11-12):1031-5. · 0.88 Impact Factor
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ABSTRACT: A rare population of leukemia cells have the properties of leukemia stem cells (LSCs) and cause resistance to therapy, but their development is not clearly understood. In the current study, we show that a higher resistance to cytotoxic drug (Ara-C) can be developed in the subpopulation of promyelocytic leukemia cells that survived radiation treatment. These drug-tolerant leukemia cells (DTLs) are not observed immediately after radiation despite extensive genetic instability in the cells, but appear in 3 weeks of recovery culture. Moreover, when the single cell-derived clones were examined by clonal trafficking, no correlation between radio-resistant and chemo-resistant leukemic clones was detected, indicating that the resistance is developed by active acquisition of the resistance without clonal predisposition. Interestingly, the DTLs mimicked the characteristics of LSCs exhibiting leukemia-initiating activities and lower levels of reactive oxygen species or a higher level expression of bmi-1 as well as higher resistance to retinoic acid-induced differentiation compared to parental leukemic cells. These studies show that an active reacquisition of stem cell-like properties can occur in the leukemia cells to develop resistance to treatments and that such reacquisition process of leukemic cells occurs in a stochastic manner triggered by radiation stress on leukemic cells.
International journal of hematology 01/2011; 93(1):27-35. · 1.17 Impact Factor
