Efficacy of total oral regimens containing ixazomib in patients with relapsed and refractory multiple myeloma / 中华内科杂志

To investigate the efficacy and safety of total oral regimen containing ixazomib in multidrug-resistant relapsed and refractory multiple myeloma(RRMM). A total of 38 patients were retrospectively analyzed from August 2018 to January 2020 in the First Affiliated Hospital of Soochow University. The overall response rate (ORR)was 36.8%. Among them, the very good partial response (VGPR) or better rate was 23.7%, and the complete response (CR) rate was 5.3%. The ORR was 41.7% in patients receiving ixazomib-lenalidomide-dexamethasone (IRD) regimen. Median PFS was 5 months and median OS was 7.5 months. The ORR was 50% after second-line therapy, 40% after third-line therapy and 12.5% after forth-line therapy or more. The ORR was 29.0% in bortezomib-refractory patients, 38.0% in lenalidomide-refractory patients, 21.4% in bortezmoib & lenalidomide dual refractory patients. Grade 3-4 hematological adverse events (AEs) were reported in 21% patients. Common hematological AEs included lymphopenia, neutropenia, thrombocytopenia. Other usual AEs were fatigue and diarrhea. No grade 3-4 peripheral neuropathy was recorded. In the treatment of relapsed/refractory multiple myeloma patients with multidrug resistance, the total oral regimens containing ixazomib demonstrate reliable efficacy and safety. Early administration of ixazomib at first or second relapse is suggested for more favorable clinical outcome.

Clinical implication of minimal residual disease monitoring by 10-color flow cytometry in multiple myeloma / 中华血液学杂志

Objective@#To evaluate the prognostic significance of minimal residual disease (MRD) monitoring by 10-color flow cytometry in multiple myeloma (MM) patients after treatment.@*Methods@#150 patients with MM who were admitted to the First Affiliated Hospital of Soochow University from July 2015 to July 2017 were retrospectively analyzed. Clinical data, MRD data monitoring by 10-color flow cytometry and prognosis were analyzed.@*Results@#39.1% (34/87) patients were MRD negative after induction chemotherapy, and 49.3% (34/69) patients were MRD negative within 1 year after autologous hematopoietic stem cell transplantation (ASCT) . MRD-negative patients after induction chemotherapy or after transplantation have better progress-free survival (PFS) than MRD-positive patients (P=0.022 and P<0.001) . According to the changes of MRD pre-ASCT and after ASCT, the patients were divided into 4 groups: patients with MRD continued negativity,improved from MRD positive to MRD negative, MRD continued positivity, transformed from MRD negative to MRD positive. The two-year PFS of the four groups were 83%, 82%, 44%, 0, respectively, (P=0.002) . Multivariate analysis showed that the level of MRD after induction chemotherapy was an independent factor for PFS (P=0.002) , HR=4.808 (95%CI 1.818-12.718) .@*Conclusion@#Patients with MRD negative after treatment is a better prognosis marker than complete remission or even the best marker, which can evaluate prognosis by combining R-ISS and cytogenetic changes.

Cytomegalovirus and Epstein-Barr virus infection after second hematopoietic stem cell transplantation in malignant hematological diseases / 中华器官移植杂志

Objective To explore the clinical features of cytomegalovirus (CMV) and EpsteinBarr virus (EBV) infection after second hematopoietic stem cell transplantation (HSCT).Methods Twenty-five patients after second HSCT from Sep.2009 to Oct.2016 were collected,and CMV and EBV DNA in peripheral blood was detected regularly by polymerase chain reaction (PCR).Factors associated were compared by univariate analysis.Results The total incidence of CMV infection was 52.0％ (13/25) after second HSCT.The incidence of CMV infection was 100％ (2/2),33.3％ (5/15) and 75％ (6/8) in bone marrow group,peripheral blood stem cell group,and mixed group,respectively.Stem cell sources were significantly correlated with CMV infection (P =0.038),however,there was no significant difference in CMV infection rate among three groups (P＞0.05).None of preconditioning regimen,GVHD prophylaxis programs or severity of aGVHD were correlated with CMV infection after second HSCT (P＞0.05).The total incidence of EBV infection was 24.0％ (6/25) after second HSCT.The incidence of EBV infection was 100％ (2/2),6.7％ (1/15) and 37.5％ (3/8) in bone marrow group,peripheral blood stem cell group,and mixed group,respectively.Stem cell sources were significantly correlated with EBV infection (P =0.008).The EBV infection rate in bone marrow group was significantly higher than that in peripheral blood group (P =0.022),however,no significant differences were found between bone marrow group and mixed group,as well as between peripheral blood group and mixed group (P＞0.05).Transplant methods were significantly correlated with EBV infection (P =0.007).The EBV infection rate in haploidentical HSCT group (71.4％) was significantly higher than that in HLA-matched sibling HSCT group (0％) and autologous HSCT group (0％) (P =0.021 and 0.028),however,no significant differences were found between any other two groups (P＞0.05).None of preconditioning regimen,GVHD prophylaxis programs or severity of aGVHD were correlated with EBV infection after second HSCT (P＞0.05).Conclusion The incidence of CMV and EBV infection in patients undergoing second HSCT is high.Stem cell sources and transplant methods are associated with CMV and EBV infection after second HSCT.

A prospective multi-center trial of non-interventional and observational study of lenalidomide in Chinese patients with multiple myeloma / 中华内科杂志

Objective To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM).Methods It was a prospective,multi-center,observational study.A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015.Relevant information was recorded,such as baseline clinical data,cytogenetic abnormalities,treatment regimens,and duration of treatment,safety,and survival.Results (1)There were 126 relapsed and refractory MM (RRMM) patients,25 newly diagnosed patients and 19 maintenance patients.The evaluable RRMM patients accounted for 120 cases,among which 74 cases(61.7％) reached the partial response (PR) or above,and a very good partial response (VGPR) in 16 patients (13.3％),a complete response (CR) in 14 cases (11.7％),a strictly complete response (sCR) in 4 cases (3.3％).Thus,a VGPR or above in 34 patients accounted for 28.3％.(2)The median follow-up was 13 months,the median time to progression 12 months.The median survival after receiving lenalidomide was 19 months,and the median overall survival (OS) was 62 months.(3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype,international staging system (ISS) Ⅰ-Ⅱ,t(4;14) negative (detected by fluorescence in situ hybridization),non-bortezomib resistance and response to previous regimens.As to OS,nonbortezomib resistance,response to previous regimens and non-primary refractoriness were positive factors.Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival (PFS),non-bortezomib resistance and non-primary refractoriness for OS.(4) Grade 3 or 4 adverse events that occurred in more than 10％ of all enrolled patients were neutropenia (12.7％),leukocytosis (11.5％) and thrombocytopenia (12.7％).Owing to intolerance of toxic side effects,7 cases withdrew lenalidomide.Conclusions No matter what combination,regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7％,a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable.In addition,the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS,non-bortezomib resistance and non-primary refractoriness for OS.Clinical trail registration Clinicaltrials.gov,NCT01947309

The clinical efficacy of the patients of acute myeloid leukemia and myelodysplastic syndromes treated with decitabine alone, combined with half or one couse of CAG regimen / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical safety and efficacy of decitabine in patients of acute myeloid leukemia and myelodysplastic syndromes (MDS/AML).</p><p><b>METHODS</b>Totally 79 patients with MDS/AML were divided into three groups: (1)Treated with decitabine alone (20 mg/m² for 5 days). (2) Combination of decitabine with half dose CAG chemotherapy (Acla 20 mg qod×3 d, Ara-C 10 mg/m² q12 h×7 d, G-CSF 300 μg/d, the dose of G-CSF adjust to the amount of blood routine). (3)Combination of decitabine with CAG chemotherapy (Acla 20 mg qod×4 d, Ara-C 10 mg/m² q12 h×14 d, G-CSF 300 μg/d, the dose of G-CSF adjust to the amount of blood routine). We observed complete remission (CR) rate, overall response rate (ORR) and overall survival (OS) of the three groups; meanwhile, we analyzed the factors relevant to decitabine efficacy and the prognosis.</p><p><b>RESULTS</b>ORR in the three groups were 53.3%, 56.5% and 69.2% respectively, with no statistically significant differences (P>0.05). Due to the last follow-up at 2014.04.01, 20 patients still survived, 45 died, 14 were lost to follow-up. The 5-year cumulative survival rate of 79 patients was 25.3%, the 2-year survival were of the three groups were 34.8%, 24.8 and 29.2% respectively with no statistically significant differences (P>0.05). Adverse events of infection and bleeding were mainly caused by decitabine. Grade 3 to 4 hematological toxicities were observed in 72 cases with the average time for the lack of granulocytes as 14.8 days. 59 patients experienced infectious events, including grade 3 or 4 infections in 14 cases, grade 1 or 2 infections in 45 cases. There were no statistically significant differences (P>0.05) among the three groups in terms of infection rates, bleeding rates, duration of neutrophenia, mean MAP transfusion and mean platelet transfusion. 79 patients were safely through bone marrow suppression by anti-infective and supportive treatment without treatment-related deaths.</p><p><b>CONCLUSION</b>Treating MDS/AML with decitabine alone, in combination with half or one course CAG regimen produced high efficacy. ORR of the combination of decitabine with one course CAG regimen was relatively higher. Three groups of patients were all well tolerated.</p>

The association of killer cell immunoglobulin like receptor gene polymorphism with cytomegalovirus infection after hematopoietic stem cell transplantation / 中华内科杂志

Objective To explore the influence of the killer cell immunoglobulin like receptor (KIR) gene polymorphism on cytomegalovirus (CMV) infection and pathogenesis after hematopoietic stem cell transplantation (HSCT).Methods The KIR genotype was determined by sequence-specific primer polymerase chain reaction (PCR-SSP) in 138 pairs of donors and recipients before HSCT during October,2005 and May,2011.Posttransplant monitoring for CMVpp65 antigen was performed by indirect immune histochemically assays since week 2 after transplantation.The differences between CMV positive group and negative group,inhibitive and active KIR of donors and recipients,and KIR haplotype frequency of donors and recipients were analyzed.Results There were no significant differences in frequency of KIR gene and haplotype AA,AB,BB between the donors and recipients.The frequencies of 2DS2 and 2DS4 * 003-007 of donors in CMV positive group were obviously lower than those in CMV negative group with significant differences(8％ vs 16％,P =0.0420;3％ vs 13％,P =0.0050).There was no significant difference in KIR gene between CMV positive group and CMV negative group.The CMV infection rates of haplotype AA,BB,AB donors were 64.38％,36.84％ and 50.00％,while CMV infection rates of haplotype AA,BB,AB recipients were 53.73％,46.15％ and 51.72％,respectively.The CMV infection rate was higher in the patients received KIR haplotype AA donor than in those received KIR haplotype BB donor (36.84％ vs 64.38％,P =0.0299).2DS4 * 003-007 and haplotype BB of donor were found associated with CMV infection in multifactor analysis.Conclusion KIR genotypes of donors are associated with CMV infection after HSCT.

Allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age / 中华器官移植杂志

Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 yeas of age. Methods From May 2002 to January 2010, 35 patients (＞ 50 years) with malignant hematological diseases received allogeneic hematopoietic cell transplantation. In 35 patients, 18 patients were conditioned with non-myeloablative regimen and 17 patients with myeloablative regimen. The outcome,engraftment and prognosis of allogeneic hematopoietic cell transplantation were analyzed. Results The hematopoetic reconstitution was achieved in 32 of 35 patients. The median time of granulocyte count exceeding 0. 5 × 109/L was 12 days and the that of platelet count exceeding 20 × 109/L was 17days. The cumulative incidence of aGVHD was 48. 6 %, and 37. 9 % patients developed cGVHD.The estimate probability of cumulative survival at 5 years was 48. 5 %, The estimate probability of cumulative mortality rate was 51.5 %, and the estimated transplant-related mortality was 22. 9 %.The relapse rate was 11.4 %. There was significant difference except for the incidence of cGVHD.Conclusion Allogeneic hematopoietic cell transplantation may be appropriate for older patients with malignant hematological diseases.