The Clinical and Molecular Characteristics of FLT3 Mutations in Chinese De Novo Adolescent and Adult Acute Lymphoblastic Leukemia Patients.

BACKGROUND: Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are frequent in acute myeloid leukemia (AML) and have important prognostic and therapeutic implications. FLT3 aberrations have been detected in a smaller fraction of acute lymphoblastic leukemia (ALL), and their prognostic value is not well established. We therefore assessed the FLT3 mutation in Chinese adolescent and adult ALL patients. PATIENTS AND METHODS: We have examined a cohort of 117 Chinese de novo adolescent and adult ALL patients enrolled between June 2016 and June 2017 from the First Affiliated Hospital of Soochow University. Prognostic factors for the ALL patient population were estimated by the Cox regression method. FLT3 mutation was detected by PCR, and its clinical effect was assessed by Kaplan-Meier curves. Differences in FLT3 mutation rate between subgroups were tested by chi-square test. RESULTS: FLT3 mutations accounted for 6.8% (8/117) in our cohort, including 3 internal tandem duplications (2.6%) and 5 tyrosine kinase domains (4.3%, 3 D835Y mutations, 1 M664I mutation, and 1 I867S mutation), which had no clinical significance on either overall survival (OS) or event-free survival. Alterations in FLT3 occurred more often in early thymic precursor (ETP)-ALL compared to non-ETP T-cell acute lymphoblastic leukemia (P = .028). However, the age at onset (P = .004), initial platelet counts (P = .018), and transplantation status (P = .007) were independent prognostic factors of OS for ALL in multivariate analysis. CONCLUSION: The FLT3 mutation was not common in Chinese ALL patients. Age at onset, platelet counts, and transplantation status rather than the presence of the FLT3 mutation were independent prognostic variables for ALL on OS in our cohort. Despite our small sample size, ETP-ALL may indicate a comparable higher FLT3-mutant rate. Because ETP-ALL has been identified as high-risk subgroup, these data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic hematopoietic stem-cell transplantation for FLT3-mutant ETP-ALL.

[Mutation Spectrum of FANCJ Gene in Adult Acute Myeloid Leukemia].

OBJECTIVE: To detect and analyze the mutation status of FANCJ gene in adult AML patients, so as to provide the basis for studying the mechanism of FANCJ driven AML and guiding the preventim and treatment of deseese. METHODS: The cDNAs were extracted and transeripted from bone marrow cells and normal skin cells in 222 newly diagnosed AML patients. The primers were designed for FANCJ gene coding region, the mutations of FANCJ gene coding region in AML patients as well as the mutations of FANCJ gene in mucous membrane epethelia in patients were detected by PCR and sanger seguencing; the evolutionary conservation of FANCJ mutation in different organisms was analyzed by NCBI Blast online bioinformaties software. RESULTS: The sequencing analysis showed that the mutations of FANCJ gene happened in 11 sites of FANCJ gene coding region, which were as followed: exon5:c.G430A:p.A144T, exon6:c.A587G:pN196S, exon9:c.C1255T:p.R419W, exon10:c.G1442A:p.G481D, exon11:c.C1609G:p.L537V, exon16:c.C2360T:p.P787L, exon17:c.C2440T:p.R814C, exon19:c.C2608T:pH870Y, exon19:c.A2686G:p.I896V, exon19:c.C2830G:p.Q944E, exon20:c.G3412A:p.D1138N. Among them, the repeatability existed in mutations of A144T, N196S, R814C, I896V and Q944E. Beside, the mutation sites of A144, R419, G381, L537, P787, H870, Q944 and D1138 were highly conserved in different organisms. CONCLUSION: Among 222 adult AML patients, the mutations of FANCJ gene have been found in 26 patients, moreover, the mutation sites are relatively conserved in different organisms, and possess important fanction. The results of this study provide the basis for exploring the mexhanism of FANCJ gene driven AML and for guiding the prevantion and treatment of AML.

Clinical Features of Chronic Graft-Versus-Host Disease Following Haploidentical Transplantation Combined with Infusion of a Cord Blood.

Our previous studies demonstrated promising outcomes after haploidentical donor transplant combined with unrelated umbilical cord blood (haplo-cord- hematopoietic stem cell transplantation [HSCT]) for hematological disorders. However, clinical profiling regarding chronic graft-versus-host disease (cGVHD) has not yet been fully described under this protocol. This study analyzed the clinical characteristics of cGVHD among 300 patients with hematological malignancies who received haplo-cord-HSCT between January 2012 and July 2016 at our center. During the follow-up, the 5-year cumulative incidence of cGVHD based on the National Institutes of Health (NIH) consensus criteria was 32.2% (95% confidence interval [CI], 28.7-35.7); the 5-year cumulative incidence of moderate to severe cGVHD was 11.4% (95% CI, 9.4-13.4). After the multivariate analysis, the GVHD overall survival (GOS) was associated with relapse, thrombocytopenia, bronchiolitis obliterans syndrome, and steroid-refractory cGVHD. The infused CD34+ cells (≥3.46 × 106/kg) from haploidentical grafts were a protective factor affecting GOS. This study proposed a nomogram for predicting GOS using the aforementioned five variables. The concordance index was 0.877 (95% CI, 0.859-0.895) for the accuracy evaluation of the nomogram. Our results suggested that the 5-year cumulative incidence of NIH-defined cGVHD after haplo-cord-HSCT was 32.2%, and this nomogram may help clinicians select reasonable treatment strategies.

The Role of FLT3-ITD Mutation on de Novo MDS in Chinese Population.

BACKGROUND: FLT3 mutations have been well-studied in acute myeloid leukemia (AML), and the detection of the FLT3 gene has become a clinical routine. However, it has not been fully analyzed in other hematologic malignancies, such as myelodysplastic syndromes (MDS). MATERIALS AND METHODS: Between 2010 and 2016, 304 adult patients with de novo MDS had the FLT3 sequence tested on their bone marrow sample. With 279 patients who had follow-up information, we also analyzed the impact of clinical and laboratory characteristics as well as FLT3 mutation status and treatment on prognosis. RESULTS: We found that the transformation rate was 3 (42.9%) of 7 patients in the FLT3-ITD-positive group, compared with 31 (10.4%) of 297 among FLT3-ITD-negative patients (P = .033). The median progression-free survival of the FLT3-ITD mutated and wild-type groups were 43 days and 363.5 days, respectively (P < .0001). The median overall survival (OS) of the 2 groups were 218 days and 410.5 days, respectively (P < .0001). We also found that 5 factors had independent prognostic impact on OS: white blood cell counts, bone marrow blast percentage, cytogenetics, transplantation status, and FLT3-ITD mutation. Furthermore, compared with the transformation group, the non-progression group was younger (P = .034), with a lower platelet count (P = .022), a lower bone marrow blast percentage (P = .001), a lower FLT3-ITD incidence (P = .007), and a longer OS (P < .0001). CONCLUSIONS: When observed at the MDS stage, patients harboring FLT3-ITD mutations had higher AML transformation rate, quicker disease progression, and shorter survival than wild-type patients. Nevertheless, once the disease progressed to leukemia, the impact of FLT3-ITD mutations on prognosis was slight. In addition, the prognosis of secondary AML was very poor whether there was an FLT3-ITD mutation or not.

Acute myopathy following intra-muscular injection of compound betamethasone: A case report.

RATIONALE: We report a case of acute steroid myopathy in a patient with eczema receiving one dose of intra-muscular injection of Compound betamethasone. PATIENT CONCERNS: Acute steroid myopathy (ASM) is usually caused by exogenous corticosteroids, and typically, occurs with therapy using intravenous corticosteroids at high doses. DIAGNOSES: The patient was considered as a diagnosis of acute steroid myopathy. INTERVENTIONS: The patient was treated with non-steroid anti-inflammatory drug and other symptomatic therapy. OUTCOMES: ASM was gradually improved after 2 weeks symptomatic treatment and completely recovered after one-month treatment. LESSONS: The diagnosis of steroid myopathy is a clinical diagnosis based on characteristic symptoms. Higher dose of steroids, especially fluorinated steroids, for longer periods of time increases the risk of steroid-induced myopathy.

[Short-term effects of citrate on markers of bone metabolism in Chinese blood donor volunteers].

This study was purposed to investigate the short-term effects of citrate administration on bone metabolism in the healthy blood donor volunteers. A crossover, placebo-controlled trial were conducted on 22 healthy blood donor volunteers. The volunteers received either a standardized infusion of citrate at 1.5 mg/(kg.min) or the equal volume of placebo normal saline, were washout for 2-3 weeks. During washout serial blood samples were collected and analyzed for bone biochemical markers and electrolytes, such as bone formation marker osteocalcin (OC), bone resorption marker carboxyterminal telopeptide of type I collagen (CTX), intact parathyroid hormone ((i)PTH), ionized calcium ((i)Ca(2+)) and phosphorus (P(i)). Serial urine samples were collected and analyzed for Ca(2+), P(i) and creatinine concentration. The results showed that compared with placebo group, infusion of citrate increased serum levels of OC and CTX (p < 0.0001). The greatest increase of OC and CTX levels occurred at the completion of the intervention. The increment of CTX was higher than OC (p = 0.02), and the OC/CTX ratio decreased (p < 0.01). Infusion of citrate also induced profound increase in serum (i)PTH level (p < 0.0001) and urinary calcium excretion (p < 0.0001), and decrease in serum (i)Ca(2+) (p < 0.0001) and P(i) (p < 0.01) levels. The decrease of (i)Ca(2+) level in female was higher than that in male (p = 0.007), but the changes of (i)PTH, OC, and CTX levels showed no differences between female and male. Changes of OC and CTX levels were closely related to each other (r = 0.56, p < 0.0001) and changes of both markers were negatively correlated with the change of serum (i)Ca(2+) concentration during the citrate intervention(r(OC) = -0.44, r(CTX) = -0.44, p < 0.0001). Increased levels of (i)PTH showed positively correlation with OC (r = 0.34, p = 0.02) and borderline correlation with CTX (r = 0.29, p = 0.06) in male. No such relationship was observed in female. All bone markers and electrolyte levels returned to baseline within 24 hours. It is concluded that the citrate load at the dose as a single platelet apheresis results in profound increase of bone turnover, which is characterized by a short-term increase of bone resorption and excretion of calcium. The possible effect of citrate on bone mass of long-term frequent platelet apheresis donor is worth concerning.