Pediatric primary central nervous system tumors registry in Thailand under National Health Security Office schemes.

BACKGROUND: Few epidemiological studies of pediatric central nervous system (CNS) tumors have been performed using data from Southeast Asian national registries. Therefore, we aimed to examine data on CNS tumors from the first national childhood CNS tumor registry in Thailand. METHODS: Newly diagnosed children with benign and malignant primary CNS tumors from 20 nationwide hospitals were included. Two eras in the Thai registry were studied to compare national protocol effectiveness, including 2003-2005 (before establishment of a pediatric CNS tumor protocol) and 2011-2012 (post-establishment). RESULTS: The first study period had 300 patients with an incidence of 7.5/1,000,000 person-years and the second had 168 patients with an incidence of 13.24/1,000,000 person-years. The three most common tumors were gliomas, medulloblastoma/primitive neuroectodermal tumor (PNET), and germ cell tumors. The most common tumor site was the cerebellum, followed by the brainstem and pineal region. Five- and 10-year overall survival (OS) rates were 46.62% (95% confidence interval [CI] 40.85-52.18) and 41.78% (95% CI 36.11-47.34), respectively, for the first period. The second period had a 5-year OS of 64.75% (95% CI 56.70-71.68). OS rates for gliomas, germ cell tumors, medulloblastoma/PNET, and ependymomas were better in the second period than in the first period. CONCLUSIONS: The incidence of primary childhood CNS tumors in our study is lower compared with other reports. Improvement of OS in the second study period might be because of establishment of the Thai Pediatric Oncology Group, and national protocols for childhood CNS tumors.

Unusual Presentation with Orbital Mass in a Child with Precursor B-Cell Acute Lymphoblastic Leukemia.

Orbital involvement is one of the extramedullary manifestations in acute leukemia. It is common in acute myeloid leukemia, but rare in acute lymphoblastic leukemia (ALL). We described a 3-year-old girl who presented with progressive proptosis of the right eye and was later diagnosed with precursor B-cell ALL. Initial blood count showed Hb 6.9 g/dL, WBC 42,000/mm3, lymphoblast 50%, and platelet count 185,000/mm3. Bone marrow aspiration revealed 90% lymphoblasts with positivity for CD10, CD19, CD20, CD22, and HLA-DR markers. Computed tomography (CT) scan of the brain and orbit revealed a homogeneous enhancing mass involving the right orbit with intracranial extension. The cytogenetic study showed 46,XX chromosomes. After 4 weeks of induction chemotherapy for very high-risk ALL, although the bone marrow was in remission, the proptosis was partially resolved. CT scan confirmed a decrease in size of the right orbital mass and degree of intracranial extension. Unfortunately, the patient abandoned the treatment after the induction chemotherapy. The actual incidence of orbital involvement in ALL is unknown. Previous case reports describe diverse manifestations of orbital involvement in ALL. The involvement may be unilateral or bilateral, may occur at first diagnosis or at relapse, and may be seen in isolation or with other systemic symptoms. There is no standard treatment protocol. Chemotherapy with or without radiotherapy is generally suggested. The role of upfront hematopoietic stem cell transplantation remains inconclusive. The previously reported prognosis of ALL with orbital involvement is poor.

A Randomized, Open-Labeled, Prospective Controlled Study to Assess the Efficacy of Frontline Empirical Intravenous Piperacillin/Tazobactam Monotherapy in Comparison with Ceftazidime Plus Amikacin for Febrile Neutropenia in Pediatric Oncology Patients.

Background: Febrile neutropenia (FN) is the most common complication in pediatric oncology patients. Appropriate empirical antibiotics treatment is essential for treatment outcome. Methods: This study was a randomized prospective controlled study to demonstrate the efficacy of piperacillin/tazobactam (PIP/TZO) monotherapy compared with ceftazidime/amikacin in children with FN. Pediatric oncology patients at Chiang Mai University Hospital, diagnosed with FN, were randomized to receive either PIP/TZO 320 mg/kg/day divided every 8 hours or ceftazidime 100 mg/kg/ day divided every 8 hours plus amikacin 15 mg/kg/day once daily. Treatment responses were compared between the two groups. Results: One-hundred and eighteen febrile neutropenic episodes in 70 patients (42 males and 28 females) were enrolled. The median age was 7 (3-10) years. The early response and complete response to initial treatment were achieved in 48/59 (81.4%) episodes and 41/59 (69.5%) episodes in PIP/TZO group compared with 40/59 (67.8%) episodes and 33/59 (55.9%) episodes in ceftazidime/amikacin group (p-value 0.091 and 0.128, respectively). Treatment modification in PIP/TZO group was required in 18/59 (30.5%) compared with 26/59 (44.1%) patients in ceftazidime/amikacin group (p-value 0.128). Similarly, the duration of fever, duration of neutropenia and duration of antibiotics treatment were not significantly different between two groups. No serious adverse events were observed. Conclusion: The treatment responses of PIP/TZO monotherapy and ceftazidime/amikacin therapy were not significantly different. Both therapies were effective for FN in pediatric oncology patients.

Pediatric non-Hodgkin lymphoma: Characteristics, stratification, and treatment at a single institute in Thailand.

BACKGROUND: In the modern era of chemotherapy, the outcome of pediatric non-Hodgkin lymphoma (NHL) continues to improve internationally. Limited data such as information on epidemiology and survival, however, are available in Asian countries. METHODS: Children (≤15 years old) diagnosed with histologically proven NHL from 1998 to 2014 were retrospectively analyzed. RESULTS: In total, 114 patients were enrolled; they were predominantly male (65.8%) and had advanced disease (stage III, IV; 71.9%). Of these, 22.8% had Burkitt lymphoma, 20.2% had diffuse large B-cell lymphoma, 21.1% had lymphoblastic lymphoma, 20.2% had large cell lymphoma, and 15.8% had peripheral T-cell lymphoma. Twenty-nine patients died, especially of uncontrolled disease (62.1%) and infection (20.7%). During a median follow up of 78.4 months, Kaplan-Meier 5 year event-free and overall survival rates were 71.5% ± 4.3% and 74.8% ± 4.1%, respectively, regardless of subtype. B symptoms (i.e. systemic symptoms of fever, night sweats, and weight loss that can be associated with both Hodgkin's lymphoma and non-Hodgkin's lymphoma) and advanced disease had a significant negative impact on 5 year survival. No other prognostic factor was found, but survival tended to have a negative correlation with age. CONCLUSIONS: Pediatric NHL is aggressive, with a high prevalence of peripheral T-cell lymphoma. The present treatment stratification seems to be effective compared with that used in developed countries.

Coinheritance of Hereditary Elliptocytosis and Deletional Hemoglobin H Disease.

Hereditary elliptocytosis is an inherited red blood cell membrane disorder characterized by typical peripheral blood smear findings of elliptocytes or rod-like red blood cells. Hemoglobin H disease is a form of α-thalassemia disease resulting in mild to moderate hemolytic anemia. The authors report 1 case of a girl who was diagnosed with oculo-auriculo-vertebral spectrum and a coinheritance of hereditary elliptocytosis and deletional hemoglobin H disease. She had moderate, non-transfusion-dependent anemia. The red blood cells showed marked poikilocytosis and fragmentation. The parents were α-thalassemia carriers and the father had the typical red blood cell morphology of common hereditary elliptocytosis.

Adverse effects of imatinib in children with chronic myelogenous leukemia.

BACKGROUND: Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor and is approved for indefinite treatment of pediatric chronic myelogenous leukemia (CML). Potential side-effects regarding growth failure and bone metabolism have been reported but data are still scarce in pediatric CML. METHODS: Six chronic-phase CML children on IM treatment with a median age of 9.87 years (range, 5.33-12.67 years) were enrolled in the study. Growth, bone mineral density (BMD), bone parameters, 25(OH)-vitamin D3 (25-OHD3) and blood tests including parathyroid hormone, insulin-like growth factor-1 (IGF-1), IGF binding protein 3, thyroid function test and sex hormones were assessed. RESULTS: Median duration of IM treatment was 78.5 months. Height velocity was suppressed during the first 30 months of treatment and improved gradually afterwards. Two patients (33.3%) had decreased lumbar spine BMD z-scores (<1.5 SD). Patients with decreased BMD had higher mean IM exposure time than those with normal BMD. The majority of patients (n = 5) had low 25-OHD3 (<30 ng/mL), but there was no correlation between BMD and 25-OHD3 status. Other blood tests were normal. CONCLUSIONS: This study supports and confirms the need for monitoring the side-effects of IM treatment on growth, bone density and vitamin D status in pediatric CML. Prolonged IM treatment was associated with low BMD without disturbing bone parameters. There was high prevalence of vitamin D insufficiency. Therefore, the beneficial effect of vitamin D supplement should be explored with regard to the effects on height velocity and BMD in CML patients with vitamin D insufficiency.

Bacteremia during neutropenic episodes in children undergoing hematopoietic stem cell transplantation with ciprofloxacin and penicillin prophylaxis.

Bacteremia during neutropenic episodes is a cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We have used oral ciprofloxacin and penicillin V, from the start of the conditioning regimen until engraftment, for the prophylaxis of bacterial infection. The objective of this study was to retrospectively analyze the prevalence of and risk factors for breakthrough bacteremia during neutropenic episodes in autologous and allogeneic HSCT patients. There were 215 patients enrolled, with a median age of 8.32 years (range 0.51-21.64 years) between 2002 and 2014. The common underlying diseases were thalassemia and acute leukemia. Bacteremia was documented in 33 patients (15.3 %), with 39 microorganisms isolated. Escherichia coli (28.2 %) and Streptococcus viridans (12.8 %) were the most commonly isolated Gram-negative and Gram-positive bacteria, respectively. Multidrug resistant strains were found in 32 and 14.3 % of Gram-negative and Gram-positive bacteria, respectively. Risk factors for bacteremia were receiving anti-thymocyte globulin (ATG) [odds ratio (OR) 2.44, 95 % confidence interval (CI) 1.06-5.65, P = 0.037] and umbilical cord blood as a stem cell graft (OR 6.60, 95 % CI 1.04-41.83, P = 0.045). In conclusion, the prevalence of bacteremia was 15.3 % and the use of ATG and cord blood were risk factors for bacteremia during neutropenic episodes.

Iron overload in non-transfusion-dependent thalassemia: association with genotype and clinical risk factors.

In the present study, we sought to determine the prevalence of iron overload in patients with non-transfusion-dependent thalassemia (NTDT) and its association with genotype and other clinical risk factors, and to evaluate the correlation between serum ferritin (SF) and liver iron concentration (LIC). Myocardial and liver iron concentration was measured by MRI using a T2* gradient multi-echo sequence in NTDT patients, aged 10-50 years. Of 91 patients, 54 (59 %) had hepatic iron overload. None had cardiac iron overload. The clinical risk factors for hepatic iron overload were age >20 years (adjusted OR 30.2, 95 % CI 4.5-203, p < 0.001), hemoglobin level <7 g/dL (adjusted OR 6.3, 95 % CI 1.01-39.5, p = 0.049), and cumulative RBC transfusion >10 units (adjusted OR 53.6, 95 % CI 3.2-884, p = 0.005). Beta-thalassemia genotype was associated with higher risk of iron overload by univariate analysis, but the association was not significant when adjusted for other clinical factors. The correlation coefficient between SF and LIC was 0.60 (p < 0.001). In conclusion, the prevalence of hepatic iron overload is high in NTDT. Older age, lower hemoglobin level, and higher cumulative RBC transfusion are significant risk factors. SF and LIC show a significant positive correlation.

Incidences, Trends and Long Term Outcomes of Retinoblastoma in Three Cancer Registries, Thailand.

BACKGROUND: Retinoblastoma (RB) is rare, albeit the most common primary intraocular malignancy among children. To elucidate the true incidence, trend and survival, we studied incidences and trends of retinoblastoma in a large population with long-term follow-up using data from 3 population-based cancer registries. OBJECTIVE: To describe the incidence, trends and survival of RB between 1990 and 2009 in Khon Kaen, Songkhla and Chiang Mai, Thailand. MATERIALS AND METHODS: We sourced the data from the cancer registries in Khon Kaen, Songkhla and Chiang Mai on children with retinoblastoma, diagnosed between 1990 and 2009. Retinoblastoma was defined as per the International Classification of Disease for Oncology version 3 using the code 9510/3. Incidence was analyzed using the standard method with the criteria of the International Association of Cancer Registries. The Kaplan-Meier method was applied to calculate cumulative survival. Trends were calculated using the log rank test. RESULTS: We identified 75 cases of children between 0 and 15 years of age diagnosed with RB (Khon Kaen 31, Chiang Mai 20, Songkhla 24). Males and females were equally affected. The most common age group was 0-4 years. The morphological verification of the disease was 90.7%. The respective ASR in Khon Kaen, Chiang Mai and Songkhla was 4.4, 4.0 and 4.6 per million; for which the overall ASR for all 3 areas was 4.3 per million. The respective trend in incidence was 4, 2.8, 5.8 and 5.4 during 1990-4, 1995-9, 2000-4 and 2005-9. Overall, incidence trended gradually upward by 2% annually. The respective survival rate in Khon Kaen, Chiang Mai and Songkhla was 50, 40 and 75% (differences not significantly different at p=0.14) and the overall survival for all centers was 60%. CONCLUSIONS: Over the last two decades, the incidence and overall survival of retinoblastoma has increased. The ASRs and survival in Thailand were less than those in resource-rich countries.

Health-Related Quality of Life in Adolescents with Thalassemia.

Children and adolescents with thalassemia suffer from chronicity of the disease and its treatment, including transfusion dependence and complications of iron overload. This study aimed to assess the health-related quality of life of adolescents with thalassemia compared with healthy controls. Sixty-four adolescents with thalassemia aged 13 to18 years and their parents were enrolled in this cross-sectional study, as well as their age- and gender-matched those of the healthy controls (64 participants and their parents). The Pediatric Quality of Life Inventory 4.0 Scales (PedsQL 4.0) self-report form was administered to the adolescents in both groups. Parents were also asked to complete the PedsQL 4.0, parent proxy-report form. The self-reported total, psychosocial, and school functioning scores of the thalassemia patients were significantly lower than those of the healthy controls (p = 0.03, 0.04, and <0.001, respectively). The parent-reported psychosocial and school functioning scores of the thalassemia group were also significantly lower than those of the controls (p = 0.03 and 0.003, respectively). Among adolescents with thalassemia, the serum ferritin level and comorbidity were the only variables associated with quality of life scores. This study showed that thalassemia negatively affected quality of life. For a better quality of life, thalassemia patients should be monitored for serum ferritin levels and treated for comorbidity as part of their comprehensive health care.

Pulmonary hypertension in non-transfusion-dependent thalassemia: Correlation with clinical parameters, liver iron concentration, and non-transferrin-bound iron.

BACKGROUND: Pulmonary hypertension is a major cardiac complication in non-transfusion-dependent thalassemia (NTDT). Several clinical and laboratory parameters, including iron overload, have been shown to have a positive correlation with the incidence of pulmonary hypertension. Non-transferrin-bound iron (NTBI) is a form of free-plasma iron that is a good indicator of iron overload. OBJECTIVES: The aim of this study was to determine the prevalence of pulmonary hypertension in patients with NTDT and to investigate its correlation with the clinical parameters, liver iron concentration (LIC) and NTBI. METHODS: Patients with NTDT were evaluated using echocardiography, and magnetic resonance imaging for cardiac T2* and LIC. Pulmonary hypertension was defined as peak tricuspid regurgitation velocity ≥2.9 m/s measured using trans-thoracic echocardiography. Clinical parameters and the status of iron overload as determined by LIC, serum ferritin, and NTBI level were evaluated for their association with pulmonary hypertension. RESULTS: Of 76 NTDT patients, mean age 23.7 ± 8.5 years, seven patients (9.2%) had pulmonary hypertension. Previous splenectomy (71.4 vs. 24.6%, P-value 0.019), higher cumulative red blood cell (RBC) transfusions (received ≥10 RBC transfusions 85.7 vs. 33.3%, P-value 0.011), higher nucleated RBCs (353 ± 287 vs. 63 ± 160/100 white blood cells, P-value <0.001), and a high NTBI level (5.7 ± 3.0 vs. 3.3 ± 2.8 µmol/l, P-value 0.034) were associated with pulmonary hypertension. There was no significant correlation between LIC or serum ferritin and pulmonary hypertension. CONCLUSION: Pulmonary hypertension in NTDT is common, and is associated with splenectomy and its related factors. NTBI level shows a significant correlation with pulmonary hypertension.

Comparative outcome of Thai pediatric osteosarcoma treated with two protocols: the role of high-dose methotrexate (HDMTX) in a single institute experience.

BACKGROUND: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). OBJECTIVES: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). MATERIALS AND METHODS: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. RESULTS: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan- Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were 43.4±6.0% and 53.2±6.1% respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [69.8±10.5%, 79.8±9.1% for MTX(+) and 31.1±6.9%, 42.2±7.4% for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol (66.7±13.6% and 15.0±8.0% for 3-year DFS, p=0.010, 73.3±13.2% and 20±8.9% for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). CONCLUSIONS: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

Vincristine-induced polyneuropathy in a child with stage I Wilms' tumour presenting with unilateral abducens nerve palsy.

A 4-year-old boy presented with right esotropia while receiving vincristine and dactinomycin for stage I Wilms' tumour according to the National Wilms Tumour Study-5 protocol. On examination, he had isolated limitation of his right lateral gaze. CT of the brain and cerebrospinal fluid examination were normal. A nerve conduction velocity study which was performed on the peripheral nerves revealed predominant motor polyneuropathy compatible with axonal loss involving the upper limbs. The patient had received a cumulative vincristine dose of 17 mg/m(2) before developing esotropia. Vincristine-induced abducens nerve mononeuropathy and subclinical motor polyneuropathy was suspected. Unilateral esotropia markedly improved after the discontinuation of vincristine and a short course of oral pyridoxine treatment.

Successful treatment of mild pediatric kasabach-merritt phenomenon with propranolol monotherapy.

Kasabach-Merritt phenomenon (KMP) is relatively rare in childhood and adolescents with high mortality rate because of its hemorrhagic complications and unresponsiveness to treatments such as corticosteroids, vincristine, intravascular embolization, and/or surgery. Propranolol, a ß -adrenergic receptor blocker, has a promising efficacy against vascular tumors such as infantile hemangiomas. But limited and variable data has been reported regarding the role of propranolol in treatment of KMP. We herein reported the successful treatment of mild pediatric KMP with propranolol monotherapy in a case of a five-week-old child with kaposiform hemangioendothelioma with successful treatment of both clinical and hematologic responses. After eight months of follow-up, patient still had stable cutaneous lesion while receiving propranolol monotherapy. Regular hematologic monitoring was done in order to detect any late relapse of the disease. Six months after discontinuation of propranolol, patient has still remained free of hematologic relapse, and primary cutaneous lesion has become a pale pink, 1 cm sized skin lesion.

Carboplatin and doxorubicin in treatment of pediatric osteosarcoma: a 9-year single institute experience in the Northern Region of Thailand.

BACKGROUND: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma because of its anti-tumor activity and had low toxicity as compared to cisplatin. OBJECTIVE: To determine demographic data, prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeutic protocol at Chiang Mai University. METHOD: A retrospective analysis was conducted on 34 osteosarcoma patients aged less than 18 years and treated between 2003 and 2011. RESULTS: Overall limb-salvage and amputation rates were 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meier analysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were 20.2±7.7% and 47.1±9.5% respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developing recurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those without initial pulmonary metastasis (28.1±13%, 63.1±12.3%, respectively, p=0.202). On univariate analysis, age at diagnosis and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. CONCLUSIONS: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis. Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen.

Cisplatin-induced ototoxicity in pediatric solid tumors: the role of glutathione S-transferases and megalin genetic polymorphisms.

Cisplatin-induced ototoxicity, an important dose-limiting side effect, has proven high interindividual variability. Glutathione S-transferases (GSTs) are isoenzymes involved in cellular detoxification processes. Megalin has been demonstrated to bind aminoglycosides, known to be similar to cisplatin for their ototoxicity. The GSTs and megalin expression is genetically polymorphic, which might be responsible for the variability in cisplatin-induced ototoxicity. The genotyping of GSTM1, GSTT1 polymorphisms, and 2 nonsynonymous single nucleotide polymorphisms (SNPs) at megalin genes, rs2075252 and rs2228171, were performed in 68 children diagnosed with solid tumors who received cisplatin-based chemotherapy. After the end of treatment, audiometry demonstrated hearing loss in 79.4% of patients according to Brock classification. The cumulative cisplatin dose >400 mg/m is associated with increased risk of cisplatin-induced ototoxicity [odds ratio (OR), 17.5; 95% confidence interval (CI), 3.09-98.62]. GSTT1 wild genotype and C-allele of rs2228171 SNPs of megalin gene occurred with higher frequency in patients with ototoxicity (P=0.023; OR, 10; 95% CI, 1.80-56.00 and P=0.034; OR, 2.67; 95% CI, 1.22-5.82, respectively). In conclusion, our results suggested that GSTT1 wild genotype and C-allele of rs2228171 SNPs might be risk factors for ototoxicity. The cumulative cisplatin dose <400 mg/m should be beneficial in order to ameliorate ototoxicity.

The second mini-transplant for unstable mixed chimerism within the first 100 days after hematopoietic stem cell transplant in severe thalassemia.

Allogeneic HSCT is the only curative treatment for severe thalassemia disease. MC occurs in one-third of these patients within the first two months after HSCT; this is a major risk factor of graft rejection, especially when RHCs are more than 25%. There is still no consensus for the management of MC, especially in the early phase of HSCT. The DLI has also been described in the treatment of MC following HSCT for hemoglobinopathies, but its success is still not guaranteed. The second HSCT has been an approach used in an attempt to cure patients who reject their graft. Concern about toxicity of conditioning regimen, the second HSCT is usually delayed for at least a year after the first HSCT. We would like to demonstrate the successful use of the second mini-allogeneic HSCT in hemoglobin E/ß-thalassemia with evidence of unstable MC in the first 100 days after allogeneic HSCT to prevent further graft loss after allogeneic HSCT.