Objective To investigate the influence of molecular targeted therapy (thalidomide,lenalidomide or bortezomib) on survival and curative effect of patients with multiple myeloma (MM).Methods The treatment of 217 patients diagnosised as MM from 1998 to 2013 were reviewed.The survival of patients who were diagnosed during different periods were compared,and the impact of improved treatment on the survival and curative effect of patients were analyzed.Results Patients who were recently diagnosed as MM after 1998 had better survival.75 patients with targeted therapy (thalidomide or bortezomib) for their early treatment had better survival compared to the patients with conventional treatments of MP/VAD.49 patients with targeted therapy after relapse or progression had a better curative effect than those with conventional treatments.16 patients had auto-ASCT or allo-SCT,and 4 of them had both auto-ASCT and allo-SCT,who had better survival than patients without transplantation.Conclusion Patients treated with molecular targeted therapy (thalidomide,lenalidomide,bortezomib) had a better curative effect and longer survival.

BACKGROUND: Diphosphonate has a predominant therapeutic effect in the prevention and treatment of postmenopausal osteoporosis. Ibandronate, as a new-type diphosphonate preparation, is gradually becoming a study hotspot.OBJECTIVE: This study is to investigate the efficiency of ibandronate in interfering postmenopausal osteoposis by observing bone mass loss related indexes in ovariectomized rats, and made a comparison with nilestriol.DESIGN: A completely randomized grouping, and controlled animal experiment.SETTING: Study Room for Bone metabolism, Fudan University Medical College.MATERIALS: Forty SD female rats, aged 10-12 months, were involved in this study. Ibandronate was provided by the State Key Laboratory of Jiangsu Institute of Atomic Medicine. Nilestriol was produced in the Shanghai 12th Pharmaceutical Factory.METHODS: This experiment was carried out in the Study Room for Bone Metabolism, Institute of Radiation Medicine,Shanghai Medical University between August 1996 and June 1998. The rats were divided into 4 groups by a lot, 10 rats in each: sham-operation group, ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group. In the sham-operation group, only small pieces of adipose tissue around the ovary were resected from the rats.Three months after operation, each rat was intragastrically administrated with 1 mL normal saline; In the ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group, each rat was subjected to bilateral ovariectomy, and 3 months later, they were intragastrically administrated with normal saline, ibandronate water solution [0.5 mg/( kg·d)] and nilestriol suspension [1 mg/(kg· time)] respectively. Each rat in the latter three groups was administrated for 90 days, twice in the first week, and then once a week.MAIN OUTCOME MEASURES: Left femur was taken out, and its dry weight and ash weight were measured. Calcium content of bone was determined with an atomic absorption spectrophotometer, bone density of the whole body with a bone density apparatus, the bone density at the juncture of 1/2 right femoral bone length with a single photon bone density apparatus, and femoral anti-bending force was determined with a universal testing machine. Alkaline phosphatase were determined by dynamical method with an automatic biochemistry analyzer, urine calcium by EDTA titration method, urine creatinine by picric kinetic method, and urinary hydroxyproline by modified proline assay.Trabecular area was calculated.RESULTS: Forty rats were involved in the final analysis. ① Bone dry weight, bone ash weight and bone calcium content in the ovariectomized group were significantly lower than those in the other 3 groups, respectively (t =13.58-52.98, P ＜0.05). ② Femoral bone density and bone density of the whole body of rats in the ovariectomized group were significantly lower than those in the other 3 groups (t =3.31-5.61, P＜0.05), while anti-bending force was close between ovariectomized group and the other 3 groups (P＞0.05). ③ The ratio of urine calcium to urine creatinine was significantly lower in the ovariectomized+ibandronate group and ovariectomized +nilestriol group than in the ovariectomized group (t =4.04, 3.30, P＜0.05). No significant difference in the alkaline phosphatase and ratio of urinary hydroxyproline to urinary creatinine existed among the groups (P ＞ 0.05). ④Trabecular area of vertebrae in the ovariectomized group was significantly smaller than that in the other 3 groups (t =2.22,2.41,3.45,P ＜ 0.05), while the trabecular area of tibia in the ovariectomized group was only smaller than that in the ovariectomized +nilestriol group (t =2.45, P＜ 0.05).CONCLUSION: Osteoporosis apPears obviously in the SD rats 3 months after ovariectomy. Ibandronate has obviously inhibitory effects on the bone mass loss of rats with postmenopausal osteoposis, and it is equivalent to nilestriol in inhibitory effect.

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

Objective:To evaluate the clinical outcomes and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a conditioning regimen based on total body irradiation (TBI) and rabbit anti-human thymocyte globulin (rATG) in the management of chemotherapy-resistant advanced peripheral T-cell lymphoma (PTCL) .Methods:Clinical data of 11 patients with chemotherapy-resistant advanced PTCL who underwent haplo-HSCT with a TBI+rATG-based conditioning regimen at the Department of Hematology, Shanghai Liquan Hospital and Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital, from September 2019 to December 2022 were retrospectively analyzed.Results:①Among the 11 patients (six males and five females), with a median age of 40 years (range: 22-58 years), there were six cases of PTCL, not otherwise specified (PTCL-NOS), three cases of angioimmunoblastic T-cell lymphoma (AITL), one case of large-cell transformation of mycosis fungoides (MF-LCT), and one case of T-cell large granular lymphocytic leukemia (T-LGLL). According to the Lugano staging system, all patients were in stage Ⅲ or Ⅳ, and eight patients had B symptoms. Before transplantation, the median number of prior lines of chemotherapy was 4 (range: 2-10), and all patients had progressive disease (PD). The median time from diagnosis to transplantation was 17 months (range: 6-36 months). ②The conditioning regimen consisted of a TBI dose of 10 Gy, administered at 2 Gy on day -8 and 4 Gy from day -7 to day -6, rATG was administered at a daily dose of 2.5 mg/kg from day -5 to day -2. Etoposide (VP-16) was given at a dose of 15 mg/kg/d from day -5 to day -4, while cyclophosphamide (CTX) was administered at a dose of 50 mg/kg/d from day -3 to day -2. In patients with central nervous system involvement, etoposide and cyclophosphamide were replaced with thiotepa (TT) at a dose of 5 mg/kg/d from day -5 to day -4. Additionally, cytarabine (Ara-C) was added at a dose of 2.0 g/m 2 twice a day from day -3 to day -2 into the conditioning. ③Successful engraftment was achieved in all patients, with a median time to neutrophil engraftment of 14.5 d (range: 11-16 d) and a median time to platelet engraftment of 13 days (range: 8-18 days). Acute graft-versus-host disease (aGVHD) occurred in one patient (grade Ⅰ-Ⅱ), and another patient experienced grade Ⅲ-Ⅳ aGVHD. Among the eight survivors, four developed chronic GVHD (cGVHD). ④Post-transplantation, nine patients achieved complete response (CR). ⑤Hematopoietic suppression occurred in all patients after conditioning, with three experiencing diarrhea, four developing mucositis, three exhibiting elevated transaminase/bilirubin levels, and seven developing infectious complications. These non-hematologic adverse events were effectively managed. ⑥At one year post-transplantation, the non-relapse mortality (NRM) was (22.5±14.0) %, the cumulative incidence of relapse (CIR) was (20.2±12.7) %, and overall survival (OS) rate was (72.7±13.4) %, and disease-free survival (DFS) rate was (63.6±14.5) % . Conclusion:TBI+rATG-based conditioning regimen for haplo-HSCT is an effective and safe treatment approach for patients with chemotherapy-resistant advanced PTCL.

Objectives:To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed.Results:Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade Ⅱ-Ⅳ aGVHD, while four (23.6% ) developed Grade Ⅲ/Ⅳ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed.Conclusions:When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.

A retrospective analysis was conducted on three patients with primary myelofibrosis who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from 2020 to 2023. They subsequently developed poor graft function. The patients received selected donor CD34 + cell boosts as salvage therapy. There were two male patients and one female patient, with a median age of 68 (39-69) years. The median time from allo-HSCT to the selected donor CD34 + cell boost was 83 (56-154) days. The median infusion of selected donor CD34 + cells was 7.67 (7.61-9.06) ×10 6/kg, with a CD34 + cell purity of 97.76% (96.50%-97.91%) and a recovery rate of 70% (42%-75%) . Hematological recovery was achieved in two cases. No acute GVHD was observed in any of the three patients. One case of moderate oral chronic GVHD was noted. Selected donor CD34 + cell boosts for the treatment of poor graft function after allo-HSCT in primary myelofibrosis was effective and no severe acute or chronic GVHD was observed.

Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Humans ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage