PERIPHERAL BLOOD CD34^+ CELL MOBILIZATION IN 42 PATIENTS WITH SEVERE AUTOIMMUNE DISEASE

Objective To evaluate the feasibility and safety of peripheral CD34+ cell mobilization in patients with severe autoimmune disease. Methods Forty-two patients underwent a total of 46 mobilizations by the regimen of cyclophosphamide 2-3 g/m2 +recombinant human granulocyte colony stimulating factor (rhG-CSF) 5 μg·kg-1·d-1. The positive selection of CD34+ cell was performed through the CliniMACS. Results In 8.1±2.3 days after administration of cyclophosphamide, the peripheral white blood cell and mononuclear cell (MNC) decreased to the lowest level. In 3.7±1.6 days after injection of rhG-CSF, the peripheral absolute MNC and CD34+ cell counts were 0.95×109/L and 0.035×109/L, respectively. After 2.4±0.6 times of leukapheresis, there gained 4.46×108/kg of MNC and 5.26×106/kg of CD34+, respectively. After mobilization, the underlying diseases were ameliorated more or less. In systemic lupus erythematosus (SLE) patients, SLE Disease Activity Index (SLEDAI) decreased from a median of 17 to 3 (P<0.01). In rheumatic arthritis patients, an American College of Rheumatology criteria for 20%(ACR20) response was achieved in all five patients. Totally, 17.4% of patients whose absolute neutrophil count <0.5×109/L suffered infection, and 31.0% of patients had bone pain after the injection of rhG-CSF. Two patients suffered severe complications, one with acute renal failure and recovered by hemodialysis, the other died of thrombotic thrombocytopenic purpura. Failed mobilization occurred in three patients. Conclusions Sufficient CD34+ cells can be mobilized by low dose of cyclophosphamide and rhG-CSF. CD34+ cell mobilization for treatment of severe autoimmune disease not only is appropriate in both effectiveness and safety but ameliorates disease also.

TAFRO Syndrome - A Specific Subtype of Castleman＇s Disease in China

To the Editor： Castleman＇s disease （CD） describes a group of lymphoproliferative disorders with heterogeneous clinical manifestations.[1] CD comprises at least two distinct diseases （unicentric CD [UCD] and multicentric CD [MCD]） with respective clinical features and prognoses： UCD often involves one lymph node area with favorable outcome： MCD is a systemic disease with relatively poor prognosis which involves multiple lymph node areas with constitutional symptoms （e.g. fever, night sweats, and weakness） and organ dysfunction. According to pathogenesis, MCD can be further divided into different subtypes based on the status of human herpes virus-8 （HHV-8） infection. Of the HHV-8 negative MCD （also named as idiopathic MCD [iMCD]）, there is a peculiar subtype named TAFRO syndrome which constitutes a constellation of unique clinical manifestations （T： Thrombocytopenia, A： Anasarca, F： myelofibrosis, R： Renal dysfunction, and O： Organomegaly）. This syndrome, first reported in Japan[2] has been reported mostly in the Japanese population and occasionally in Caucasians. There is no such case reported in China. We herein report the first patient with TAFRO syndrome in China with confirmed myelofibrosis.

Primary central nervous system lymphoma:status and advances in diagnosis,molecular pathogenesis,and treatment

Primary central nervous system lymphoma(PCNSL)is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes.This article aims to present a brief profile of PCNSL diagnosis and treatment in immunocompetent patients.The authors retrieved information from the PubMed database up to September 2019.The annual incidence of PCNSL increased over the last four decades.The prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate,which is now the backbone of all first-line treatment polychemotherapy regimens.Gene expression profiling and next-generation sequencing analyses have revealed mutations that induce activation of nuclear factor-kB,B cell antigen receptor,and Janus kinases/signal transducer and activator of transcription proteins signal pathways.Some novel agents are investigated in the treatment of relapsed PCNSL including immunotherapy and targeted therapy.In particular,lenalidomide and ibrutinib have demonstrated durable efficiency.Treatment of PCNSL has evolved in the last 40 years and survival outcomes have improved in most patient groups,but there is still room to improve outcome by optimizing current chemotherapy and novel agents.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study

Background:Bendamustine was approved in China on May 26th,2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma(NHL).The current study was the registration trial and the first reported evaluation of the efficacy,safety,and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.Methods:This was a prospective,multicenter,open-label,single-arm,phase 3 study(NCT01596621;C18083/3076)with a 2-year follow-up period.Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles(and up to eight cycles).The primary endpoint was the overall response rate(ORR);and secondary endpoints were duration of response(DoR),progression-free survival(PFS),safety,and pharmacokinetics.Patients were classified according to their best overall response after initiation of therapy.Proportions of patients in each response category(complete response[CR],partial response[PR],stable disease,or progressive disease)were summarized along with a twosided binomial exact 95%confidence intervals(CIs)for the ORR.Results:A total of 102 patients were enrolled from 20 centers between August 6th,2012,and June 18th,2015.At the time of the primary analysis,the ORR was 73%(95%CI:63%–81%)per Independent Review Committee(IRC)including 19%CR and 54%PR.With the follow-up period,the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment;the median PFS was 18.6 months and 15.3 months,respectively.The most common non-hematologic adverse events(AEs)were gastrointestinal toxicity,pyrexia,and rash.Grade 3/4 neutropenia was reported in 76%of patients.Serious AEs were reported in 29 patients and five patients died during the study.Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.Conclusion:Bendamustine is an active and effective therapy in Chinese patients with relapsed,indolent B-cell NHL,with a comparable risk/benefit relationship to that reported in North American patients.

Well-differentiated systemic mastocytosis with KIT K509I mutation and uterus infiltration in an Asian woman with good response to imatinib

To the Editor: We report a 27-year-old woman with a 2-month history of irregular uterine bleeding between periods. Blistering on the head was noted in the patient at the age of 2 months, and she gradually developed red maculopapular lesions over her neck and back during puberty, which were itchy after exposure to physical friction. On admission, physical examination had revealed diffuse faint maculopapular rash mainly on the neck and back [Figure 1]. Pelvic examination showed a smooth red lump (5 cm) on the cervix. No abnormality was detected in the complete blood count. Afterwards, the cervical lump was resected and confirmed to be the infiltration of mature mast cells (MCs) after careful pathological investigation. Additionally, a skin nodule biopsy also indicated mass aggregation of MCs, and a bone marrow (BM) biopsy showed a mass of round MCs with abundant cytoplasmic granules. The MCs accounted for about 22.5% of all cells in the aspirate smears. Flow cytometry immunophenotypic analysis on BM suggested that an aberrant MC population had represented 10% of the total analyzed cells, which was positive for CD117, CD33, and CD9, partially positive for CD2 and CD68, and negative for CD25. Genetic test through exome-wide sequencing for the receptor tyrosine kinase (KIT) gene had revealed K509I mutation.