Geritinib in the targeted therapy of acute myeloid leukemia with FLT3 mutation: report of 5 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of geritinib in the treatment of acute myeloid leukemia (AML) with FLT3 mutation.Methods:The clinical data of 5 AML patients with FLT3 mutation who were diagnosed in the University of Hong Kong-Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Second People's Hospital, Shenzhen University General Hospital from March 2020 to April 2021 were retrospectively analyzed. Relapsed patients concurrently received two- or three-drug chemotherapy combined with geritinib. Blood routine was checked once a week; liver function and renal function were checked once every 2 weeks during treatment. Bone marrow puncture was performed once every 1 to 3 months to monitor the bone marrow morphology, minimal residual disease (MRD) and FLT3 mutation expression levels. The efficacy, side effects, overall survival of these patients were analyzed after treatment with geritinib.Results:The white blood cell was increased in all the 5 patients at the initial diagnosis. FLT3 mutations analysis showed FLT3-internal tandem duplication (ITD) (3 cases) and FLT-3 tyrosine-kinase domain (TKD) (2 cases). Among 5 patients, 1 patient was relapse-free with maintenance therapy of oral geritinib after hematological stem cell transplantation (HSCT) for 60 days; among other 4 relapsed and refractory patients, 1 female patient after pregnancy relapsed after transplantation and then achieved complete remission followed by the maintenance therapy with geritinib after oral geritinib, 1 16-year-old patient achieved treatment outcome close to the complete remission after treatment with geritinib, 1 patient achieved complete remission after treatment with geritinib, and then underwent haplo-HSCT followed by the maintenance therapy with geritinib and the other 1 relapsed patient achieved complete remission after treatment with geritinib. After transplantation, 3 patients receiving maintenance treatment of geritinib did not relapse. The main side effects included anemia, decreased neutrophil count, rash, and increased aminotransferase. The median follow-up time of 5 patients was 15 months (6-20 months). All 5 cases survived until the last follow-up in November 2021 and 4 patients were disease-free.Conclusions:Relapsed and refractory AML patients with FLT3 mutation can achieve complete remission after treatment with geritinib and get a chance for transplantation. Geritinib may reduce the risk of recurrence after transplantation and improve survival rate. No serious side effects occur in geritinib treatment.

Clinical observation of primary extranasal nasal-type NK/T cell lymphoma treated with P-GEMOX as a first-line regimen / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy of P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) as a first-line regimen for the treatment of primary extranasal nasal-type NK/T cell lymphoma (NKTCL).Methods:The clinical manifestations, treatment response and prognosis of 7 patients with primary extranasal nasal-type NKTCL who underwent P-GEMOX chemotherapy as a first-line therapy in Shenzhen People's Hospital from September 2015 to October 2018 were retrospectively analyzed.Results:The median age of 7 patients with primary extranasal nasal-type NKTCL was 41 years old (27-74 years old), which was more commonly found in males (6 cases); the primary and invading extranasal sites included ileocecal, lymph nodes, skin, testis, adrenal gland, central nervous system, etc. The P-GEMOX regimen was used as a first-line therapy, although some patients had a short-term effect, all patients eventually progressed rapidly and died. The overall survival time was 2 weeks to 21 months.Conclusion:The short-term efficacy of P-GEMOX as a first-line therapy for the treatment of primary extranasal nasal-type NKTCL is acceptable, but the long-term efficacy is poor.

Chinese family with congenital Dysfibrinogenemia carries a heterozygous missense mutation in FGA: Concerning the genetic abnormality and clinical treatment

Objectives: Congenital dysfibrinogenemia is a rare hereditary disease characterized by normal antigen level but lower function level of fibrinogen. Patients with congenital dysfibrinogenemia usually present as bleeding and/or thrombotic events. In this study, we explored the genetic abnormality and clinical treatment of a Chinese family with dysfibrinogenemia

Methods: This study was conducted in Jan 2015 to Jan 2016 in the Second Medical College [Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong Province, P.R. China. Coagulation function test were used to screen patients in this family. For all family members, DMA from peripheral blood was isolated. Whole-genome exon sequencing was carried out to screen possible mutations. And sanger sequencing was employed to further confirm the mutation in patients

Results: The proband is a woman who had anemia and increased menstruation. Hypofibrinogenemia was found after admission. However, a pulmonary embolism occurred after the fibrinogen replacement treatment. Whole exon sequencing was conducted afterward. A candidate mutation in FGA gene [c.103C>A] was identified and validated in the woman and in two siblings

Conclusion: From this case, we learned that 1] point mutation of c. 103C>A is the pathogenesis for congenital dysfibrinogemia in this family; 2] thromboprophylaxis should always be in consideration when fibrinogen replacement is conducted. Prospective studies are needed to determine the best fibrinogen replacement strategy in order to achieve adequate hemostasis while minimize risk of thrombosis

Blastic plasmacytoid dendritic cell neoplasm: a case report and literature review / 白血病·淋巴瘤

Objective To provide new information for treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN).Methods Through one case report and literature review of 48 BPDCN cases were reviewed retrospectively.The clinical characteristics,treatment choices and prognosis were analyzed.Results BPDCN patients were mainly elderly males,mostly presented as skin rash and bone marrow infiltration.Immunophenotype was characteristically expressed as CD4,CD56 and CD123.Lymphoid-like regimens could induce higher response rate,lower relapse rate and longer overall survival compared with myeloid-like regimens.Allogeneic hematopoietic stem cell transplantation may provide long-term survival.At the onset of the disease,The counts of white blood cells (WBC) and blood platelet (Plt) may be correlated with inferior overall survival.Conclusions BPDCN is a disease with distinct clinical characteristics and immunophenotype.Lymphoid-like regimen may be the better treatment of choice,while allogeneic hematopoietic stem cell transplantation should be taken into account in the first complete remission for longterm survival.

Therapeutic effects of low-dose,ultra-low-dose and standard-dose chemotherapy for elderly acute myeloid leukemia / 白血病·淋巴瘤

Objective To evaluate the therapeutic effect of low-dose,ultra-low-dose and standard dose chemotherapy for elderly acute myeloid leukemia.Methods A retrospective analysis was performed on 77 elderly AML patients aged 60 years or older.The short-term and long-term effects were compared among low-dose,uhtra-low-dose and standard-dose chemotherapy.Results Although patients receiving low-dose or ultra-low-dose chemotherapy were older,with higher PS scores and lower WBC count,there were no significant differences in CR rate,ORR,EFS or OS between patients who received low-dose/ultra-low-dose chemotherapy and standard-dose chemotherapy.By dividing the total samples into subgroups according to age or PS scores,we found out that patients younger than 70 or with a PS score less than 2 showed a much better prognosis,no matter short-term or long-term,in low-dose／ultra-low-dose group rather than in the standard dose group.While in those patients older than 70 or with a PS score more than 2,the differences between those two groups were not significant.Further analysis showed that low-dose chemotherapy did not reduce treatment related mortality,neither did it increase the risk of long-term relapse.Conclusion Low-dose and ultra-low-dose chemotherapy can improve the prognosis of elder AML patients compared with standard-dose chemotherapy,especially for elderly patients who have a better general state.