Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis / 中华血液学杂志

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

The Role of Whole Body DWI in the Evaluation of Bone Disease in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the characteristics of ADC value changes in DWI of newly diagnosed symptomatic MM patients and its correlation with R-ISS stage.@*METHODS@#The data of 148 newly diagnosed symptomatic MM patients treated by whole-body DWI scan at The First Affiliated Hospital of Soochow University from June 2016 to June 2019 were selected and retrospectively analyzed and 30 cases of age-matched healthy people were selected as controls. The differences of ADC values between the patients in normal control group, DWI- group and DWI+ group were compared, and the relationship between ADC values and R-ISS stage in MM patients was compared.@*RESULTS@#The plasma cell percentage of the patients in DWI+ group was higher than those in DWI- group. ADC values of vertebra, sternum, rib, pectoral girdle, pelvic girdle of the patients in DWI+ group were significantly higher than those in DWI- group and normal control group. The ADC values of each part of the patients in DWI- group were higher than those in normal control group. ADC values of sternum, rib and pectoral girdle in the patients at R-ISS stage III were higher than those at R-ISS stage I and II, while, there was no statistical difference between R-ISS stage I and II groups. And there was no significant difference in ADC values of other bone parts such as vertebra and pelvic girdle in patients at R-ISS stage Ⅰ-Ⅲ.@*CONCLUSION@#DWI+ in MM patients is related to higher tumor invasion. The ADC values of the DWI+ group are higher than those of the DWI- group; the bone ADC values of the DWI- patients are still higher than the normal ones. And there is a certain relationship between ADC value and R-ISS stage.

The Effects of Chidamide Combined with Anti-myeloma Drugs on the Proliferation and Apoptosis of Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of chidamide combined with anti-myeloma drugs on the proliferation and apoptosis of myeloma cells.@*METHODS@#The proliferation inhibition of the cells was detected by CCK-8 method, and flow cytometry was used to detected the apoptosis of the cells.@*RESULTS@#Chidamide could inhibit the proliferation of myeloma cells and promote the apoptosis of primary myeloma plasma cells in a time- and dose-dependent manner (P<0.05). In NCI-H929 cell line, chidamide combined with low-dose bortezomib and lenalidomide showed synergistic effect, while combined with dexamethasone and pomalidomide showed additive effect. In MM.1s cell line, chidamide combined with bortezomib, dexamethasone, lenalidomide and pomalidomide all showed synergistic effects.@*CONCLUSION@#Chidamide inhibits proliferation of myeloma cells in a time- and dose-dependent manner and promotes apoptosis of primary myeloma plasma cells. Furthermore, it can enhance the inhibitory effect of anti-myeloma drugs.

Application of Conditioning Regimen with Busulfan and Cyclophosphamide in Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the safety and efficacy of BUCY (busulfan and cyclophosphamide) conditioning regimen for autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 72 MM patients received transplantation in the Hematology Department of the First Affiliated Hospital of Soochow University from May 2012 to June 2015 were retrospectively analyzed. Among them, 36 patients received BUCY conditioning regimen while the others received high-dose melphalan (HDM) conditioning regimen. The complication, post-transplantation hematopoietic reconstitution and efficacy between the two groups were compared.@*RESULTS@#There were no significant differences in sex, age, isotype, stage, induction therapy, mobilization method and proportion of conditioning regimen with Bortezomib between the two groups. The median time of neutrophil engraftment for the patients in BUCY and HDM groups was 10 (8-17) and 10 (9-13) d (P=0.046), and the median time of platelet engraftment was 10 (8-18) and 11 (9-47) d (P=0.017), respectively. The transplant related mortality of the patients in both groups was 2.7%. The CR rates of the patients after ASCT (38.9% and 50.0%) were higher than those before ASCT (27.8% and 19.4%) in the two groups. For the patients in BUCY group, the median follow-up time was 45 (0-61) months. Fifteen patients (41.7%) achieved disease progression. While for the patients in HDM group, the median follow-up time was 52(0-75) months. Twenty-two patients (61.1%) achieved disease progression.@*CONCLUSION@#The BUCY conditioning regimen is a safe and effective therapy for ASCT in patients with MM. Besides, in terms of safety and efficacy, BUCY regimen is not inferior to HDM regimen. BUCY regimen may replace HDM regimen as a standard conditioning regimen for ASCT in MM.

Clinical characteristics of healthcare-associated infection in initially treated patients with multiple myeloma during the induction period / 中国感染控制杂志

Objective To explore the infection status and clinical characteristics of healthcare-associated infection (HAD in patients initially diagnosed with multiple myeloma(MM) during the induction period.Methods Clinical data of 116 patients diagnosed with MM and initially treated with PAD(bortezomib + adriamycin + dexamethasone)or PDD(bortezomib + liposome doxorubicin + dexamethasone) regimen in a hospital were collected,infection rates and clinical characteristics of patients during the induction therapy period were analyzed statistically.Results Among 116 patients,69 received PAD regimen,and 47 received PDD regimen,infection rates in two groups were 79.7％ and 89.4％ respectively;73 patients received subcutaneous injection of bortezomib,43 received intravenous injection of bortezomib,infection rates in subcutaneous injection group and intravenous injection group were 78.1％ and 93.0％ respectively,difference was statistically significant between two groups(P＜0.05).During the induction period,HAI rate was 83.6％ (n =97),81 patients developed infection during the first course,infection status of 3 patients were not clear due to therapy outside the hospital,the actual infection rate was 71.7 ％ (81/113);infection rate during the second course was 56.6 ％ (64/113);a total of 98 patients completed three therapy courses,infection rate was 43.9％ (43/98);66 patients completed four therapy courses,infection rate was 28.8％ (19/66).With the increase of the therapy course,infection rate showed a downward trend.Infection sites from high to low were respiratory system,skin and mucosa,oral and gastrointestinal system,bloodstream,and urinary tract.Difference in constitute of clinical diagnosis between patients receiving and without receiving prophylactic antifungal agents during chemotherapy period was not statistically significant (P =0.063).Conclusion Infection rate is very high during induction period,the main infection site is respiratory system,clinicians and patients need to pay more attention to the prevention and treatment of respiratory system infection.

Clinical and laboratorial analysis for 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or positive BCR-ABL / 中国实验血液学杂志

The purpose of this study was to summary the clinical and laboratorial features in 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or BCR-ABL fusion gene positive (Ph(+)MPAL), 15 adult patients with Ph(+)MPAL were defined by WHO-2008 classification. The clinical characteristics, results of morphology, immunology, cytogenetics and molecular genetic detections and results of follow-up in 15 adult patients with Ph(+)MPAL were analyzed retrospectively. The results showed that 15 patients among 87 cases of MPAL demonstrated Ph(+)MPAL (17.2%; 15/87) (7 males and 8 females), their median age was 51 (range 16-81) year old and median WBC count at diagnosis was 69 (12.7-921)×10(9)/L. Based on FAB criteria, these patients showed different morphologic types, including AML (13.3%; 2/15), ALL (40.0%; 6/15), HAL (46.7%; 7/15). Immunologic analysis indicated that 15 cases of Ph(-)MPAL were all classified as B-lymphoid +myeloid mixed immunophenotype. Except one patient, all expressed CD34 antigen on the surface of leukemia cells with 64.3% strong positive, only Ph (53.3%; 8/15), Ph with additional chromosomal abnormalities (33.3%; 5/15) and normal karyotype (13.3%; 2/15) were cytogenetically identified. BCR-ABL fusion gene transcript positive were detected by multiplex reverse transcription PCR in all cases, with e1a2 subtype (p190) (40.0%; 6/15) and b2a2 or b3a2 (p210) subtype (60.0%; 9/15). Four out of 7 (57.1%) patients were found to have IKZF1 gene deletion, without other common gene mutations. Seven out of 10 cases (70.0%) achieved complete remission (CR) after one cycle of induction chemotherapy. In the induction stage, CR rate seemed higher when tyrosine kinase inhibitors (TKI) were added to chemotherapy (83.3%:50.0%; P = 0.206). Overall survival (OS) in 4 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was longer than that in 4 patients received chemotherapy alone (P = 0.004). It is concluded that Ph(+)MPAL mainly is expressed as B+My phenotype. The majority of patients is older and has CD34 overexpression. In the aspect of molecular genetics, the Ph(+)MPAL is similar to other acute leukemia with Ph chromosome. Ph(+)MPAL is a subtype of acute leukemia with poor prognosis. WBC count at diagnosis is an independent prognostic factor. The combination of TKI and allo-HSCT can improve their long-term survival, which needs to be confirmed through carrying out a prospective and multicenter clinical trial for newly diagnosed Ph(+)MPAL.

Analysis of NPM1 gene mutations in acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the prevalence of nucleophosmin (NPM1) gene exon 12 mutations in adults with acute myeloid leukemia (AML) and its clinical characteristics.</p><p><b>METHODS</b>Genomic DNAs from 101 AML adults were screened by PCR and sequencing or capillary electrophoresis (CE) for NPMI mutations.</p><p><b>RESULTS</b>NPM1 exon 12 mutations were present in 31.7% of the overall cohort, including 1/1 (100%) of M0, 9/17(52.9%) of M1 , 7/25 (28.0%) of M2, 0/23(0%) of M3, 2/7 (28.6%) of M4 and 13/25 (52.0% ) of M5. NPM1 gene mutations were more prevalent in patients with normal karyotype (27/59, 45.8%) compared with that in those with karyotypic abnormalities (5/42, 11.9% ) (P < 0.001). NPM1 mutant cases were significantly associated with old age (P < 0.05), high peripheral white cell count (P < 0.05) and low expression of CD34 (P < 0.05) and CD17 (P<0.05). Sequence analysis of these NPM1 mutant cases revealed 5 known mutations (type A, B, D, N(M), and P(M)) and 1 novel variant (named as type S).</p><p><b>CONCLUSIONS</b>NPM1 exon 12 mutations occur with a considerable percentage in AML patients with normal karyotype, M1/M5 subtype and older age, and are associated with higher peripheral white cell count and lower expression of CD34 and CD117.</p>