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Purpose: In this study, we analyzed the short term change of thyroid function, incidence and risk factors of thyroid dysfunction soon after allogeneic hematopoietic stem cell transplantation(HSCT) in children. Method: We enrolled 80 pediatric patients following allogeneic HSCT, at the Catholic HSCT center between January, 2004 and February, 2006. Serum TSH(thyroid stimulating hormone), total serum thyroxine, total serum triiodothyronine levels were systematically measured in 80 patients before and 1 month, 6 month and 12 month after HSCT. Results: Thyroid function was statistically decreased at 1 month after HSCT( P < 0.001). Thyroid dysfunction at 1 month was observed in 43(54%) of 80 patients, 31(39%) of whom presented with euthyroid sick syndrome. Thyroid dysfunction was normalized within 1 year after HSCT(Table). In univariate analysis, malignant disease and presence of acute GvHD(grade ≥II) were risk factors for euthyroid sick syndrome( P = 0.04, 0.01). In multivariate analysis, we could not detect an independent risk factor for euthyroid sick syndrome( P = 0.19, 0.06). Conclusion: The present study suggests that the incidence of thyroid dysfunction is high after allogeneic HSCT. Therefore, regular monitoring of thyroid hormone levels after HSCT is required. | | Pre HSCT | Post HSCT 1 month | Post HSCT 6 month | Post HSCT 12 month | |:-----------:| --------- | ----------------- | ----------------- | ------------------ | | T3 (ng/dL) | 161 ± 27 | 100 ± 35 | 123 ± 35 | 124 ± 35 | | T4 (μg/dL) | 8.7 ± 1.6 | 6.5 ± 2.4 | 7.3 ± 1.8 | 7.7 ± 1.6 | | TSH (mIU/L) | 2.9 ± 1.9 | 1.2 ± 1.3 | 2.4 ± 1.8 | 2.1 ± 1.3 | Short-term changes in thyroid function after HSCT

Immunosuppressive therapy (IST) has been extensively used as first line treatment in children with severe aplastic anemia (SAA), who do not have a suitable donor for hematopoietic stem cell transplantation (HSCT). Several studies have reported that androgens may enhance the response to IST. We retrospectively investigated the effects of androgen on survival. The patient population consisted of 112 children with diagnosis with SAA at St. Mary’s Hospital between 1991 and 2004. All patients received horse type anti-lymphocyte (ALG) or rabbit type anti-thymocyte globulin (ATG), and methylprednisolone, cyclosporin A without G-CSF. Forty-seven children began oral administration of oxymetholone (OMT, 2mg/kg/day) at post-IST 4 weeks for 3 months. We assessed response at post-IST 4 weeks, 6 months on the basis of Camitta’s criteria. Treatment failure was defined as transfusion dependency, death, clonal evolution, and progression to HSCT. We analyzed failure free survival (FFS) and overall survival (OS) in childhood SAA treated with IST. There were no differences in patient characteristics but children treated with ALG received more OMT than those treated with ATG (P < 0.01). The response rate at post-IST 6 months was 57.1%, 24.1% showing a complete response (CR) and 33.0% a partial response (PR). A high CR rate was identified in those treated with OMT administration (P = 0.04). Factors associated with response to therapy were type of anti-globulin utilized, response at post-IST 4 weeks, and the administration of OMT (P < 0.01). The relapse rate was 40.6%, and was noted to be higher in those given ALG. The OS and FFS in this study was 77.6 ± 4.3% and 54.5 ± 5.1% respectively at 8 year. Factors associated with FFS were response at post-IST 6 months (P < 0.01, RR: 2.155, 1.246 ~ 3.728) and the administration of OMT (P = 0.04, RR: 1.830, 1.026 ~ 3.265) in multivariate analysis, although type of anti-globulin was also included in univariate analysis. The FFS was higher in those treated with OMT (74.3 ± 6.4%) than those who were not given OMT (33.5 ± 7.3%) at 8 year. With regards to the type of response, the FFS was higher in those administered OMT (80.0 ± 10.3%) than those not given OMT (26.4 ± 14.9%) (P = 0.02, RR: 2.273, 1.1624 ~ 12.064) amongst patients who showed PR, although there was no significant difference in FFS amongst patients who showed CR with OMT (94.7 ± 9.0%) or without OMT (83.3 ± 15.2%) at 8 year (P = 0.76). The factor associated with OS was response at post-IST 6 months (P = 0.013, RR: 3.30, 1.28 ~ 8.52) in multivariate analysis, although severity at diagnosis was also included in univariate analysis.Our data revealed that OMT improved FFS in childhood SAA responding to IST, especially in those with PR. In this retrospective study, we concluded that the addition of short term OMT to IST as first line therapy significantly improved CR rate and FFS in childhood SAA patients without a suitable HLA-matched donor.

Background: Several approaches using antibodies to CD33 in the treatment of relapsed or refractory AML have been attempted, including the use of gemtuzumab ozogamicin. We decided to conduct a pilot study in pediatric patients with CD33 positive relapsed or refractory AML of targeted immunotherapy with GO combined with FLAG-IDA, to determine whether this combination would be effective and well tolerated. Patients and Methods: Eligibility criteria included CD33 positive relapsed or refractory AML and baseline serum bilirubin and creatinine ≤ 1.5 mg/ml. The patients received GO on day 1 of the course. FLAG-IDA consists of idarubicin, fludarabine, cytarabine, and G-CSF. Toxicity was assessed using the National Cancer Institute common toxicity criteria. Complete response (CR) was defined as less than 5% blasts on a bone marrow aspirate of adequate cellularity showing evidence of trilineage regeneration with a peripheral ANC to 1.0×109/l and platelet count to 100×109l. CRp was defined as a response with incomplete platelet recovery but platelet transfusion independence. Overall response (OR) was calculated by adding CR and CRp rates. Results: Between September 2005 and January 2006, five patients received GO with FLAG-IDA up to 3 infusions. All patients received GO doses of 3 mg/m2 for induction which reduced to 0.75–1.25 mg/m2 for consolidation. Median age was 9.7 (3.3–16.1) years and there were 4 boys and 1 girl. The median interval between initial diagnosis and GO administration was 1.2 (0.5–3.1) years. Three patients were relapsed state after stem cell transplantations (2 UCBT, 1 sibling BMT), 1 patient was refractory state and 1 patient was relapsed state after chemotherapy. Most common infusion-related reactions were fever and transient elevations of liver transaminases and bilirubin were noted, but VOD was not observed. The median number of days required to reach an ANC of more than 0.5×109/l were 30 (21–51) days and spontaneous platelet recovery to more than 20×109/l was 48 (9–60) days. Overall response rates were 80% and 1 patient was refractory state and 1 patient died of TMA after subsequent UBMT. Conclusion: GO with FLAG-IDA was a valuable treatment option for children with relapsed or refractory CD33 positive AML. No cases of VOD occurred in our series, even after SCT in two responders. GO with FLAG-IDA was well tolerated, even during repeated infusions. Treatment responses and outcomes UPN Course ANC, recovery 0.5×109/l, 1×109/l (d) PLT, revocery 20×109/l, 100×109/l (d) Response Further Treatment Treatment outcomes 1 1 37, 41 49, NR CRp None Alive with disease free (342 days) 2 48, 51 60, NR CRp 3 51, 58 51, 143 CR 2 1 30, 31 35, 40 CRp UBMT Died of TMA (251 days) 2 33, 35 48, NR CR 3 1 21, 24* 9, 16* CR DLI Alive with disease free (289 days) 4 1 31, 31 NR, NR Refractory Supportive treatment Alive with refractory AML(251 days) 2 27, NR NR, NR Refractory 5 1 24, 25 28, 31 CR 2nd UCBT Alive with disease free (214 days) 2 23, 24 26, 27 CR