Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study / 中华血液学杂志

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

Geriatric Assessment to Predict Survival and Risk of Serious Adverse Events in Elderly Newly Diagnosed Multiple Myeloma Patients: A Multicenter Study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Elderly multiple myeloma (MM) patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival (OS) time and side effects with elderly patients are unclear in China. The study tried to find out the role of geriatric assessment in the Chinese elderly MM.</p><p><b>METHODS</b>We retrospectively analyzed the data of 628 newly diagnosed patients from six hospitals from June 2011 to June 2013. A geriatric assessment had been performed to assess comorbidities, cognitive, and physical status for these patients. The primary endpoint was to evaluate different physical states of elderly patients with OS time and treatment-related side effects.</p><p><b>RESULTS</b>An additive scoring system (range: 0-5), based on age, Katz's Activity of Daily Living (ADL) and Lawton's Instrumental Activity of Daily Living (IADL) ≤5 and Charlson Comorbidity Index (CCI) was developed to identify three groups: fit (score = 0); intermediate-fitness (score = 1); and frail (score ≥2). The 3-year OS was 63% in fit patients, 63% in intermediate-fitness patients, and 49% in frail patients ≥3 hematologic adverse events (AEs) were documented in 45 (35.4%) fit, 34 (34%) intermediate-fitness, and 121 (30.2%) frail patients. The risk of a grade ≥3 hematologic AEs was not significantly increase in intermediate-fitness (hazard ratios [HR]: 0.99, 95% confidence interval [CI]: 0.54-1.47, P = 1.000) and in frail patients (HR: 1.16, 95% CI: 0.70-1.93, P = 0.558) compared with fit ones.</p><p><b>CONCLUSIONS</b>MM occurs earlier in life and being advanced when the diagnosis is made in the mainland of China. The overall survival in frailty with International Staging System (ISS) II/III was the worst in all patients.</p>

Multiple myeloma with rupture of ovarian plasmacytoma / 中华医学杂志(英文版)

Multiple myeloma is a clonal proliferation of plasma cells with multiple osteolytic lesions. Extramedullary dissemination of multiple myeloma in ovary is relatively uncommon. A 54-year-old female patient, diagnosed as multiple myeloma three years ago, was admitted to the hospital for the complaints of intermittent abdominal pain for three days. The vaginal gynecological ultrasound showed celiac solid mass. The emergent laparotomy showed a significantly enlarged right cystic ovary and the pathological reviews showed ovarian plasmacytoma. The final diagnosis of this patient was ovarian extramedullary plasmacytoma rupture and bleeding.

Effects of bortezomib combined with methylprednisolone in treatment of 33 cases of relapsed or refractory multiple myeloma / 中国实验血液学杂志

The aim of this study was to explore the clinical effect and toxicity of bortezomib combined with methylprednisolone in treatment of relapsed or refractory multiple myeloma (MM). Clinical data of 33 patients (23 male, 10 female; aged from 38 to 85 years old) were analyzed retrospectively. The median diagnosis time was 25 (2 - 120) months. 33 patients received bortezomib (0.9 - 1.1) mg/m(2) on days 1, 4, 8, 11, in combination with methylprednisolone 40 mg/d (4 cases), 80mg/d (13 cases), 120 mg/d (2 cases), 200 mg/d (9 cases), 300 mg/d (5 cases) respectively. The median follow-up time was 10(3-60) months. The used therapy courses were 1 - 8 (mean 4 courses). The results indicated that 24 cases showed the response of different degree, the overall response rate (ORR) was 72.7% (24/33). 32 patients received ≥ 2 therapy courses, and ORR was 71.9% (23/32). 16 patients received 4 therapy courses, and ORR was 93.8% (15/16 cases). 7 patients received 6 therapy courses and the ORR was 100% (7/7 cases). Main side-effects were thrombocytopenia, infection and peripheral neuropathy. The median survival time was 41.5 (2 - 120) months and the 2-year, 3-year and 5-year overall survival rate were 80%, 59.1% and 21.1%, respectively. It is concluded that bortezomib combined with methylprednisolone is an effective therapy with higher response rate, and safe in treatment of relapsed or refractory multiple myeloma.

Multiple myeloma complicated with spinal infiltration / 中国实验血液学杂志

This study was aimed to investigate the clinical features of multiple myeloma (MM) complicated by spinal infiltration (extramedullary plasmacytoma) so as to enhance the understanding of this kind of MM and reduce the missed diagnosis for these MM patients. 10 patients with MM complicated by spinal infiltration were enrolled in this study. Bone marrow, blood, hepatic and renal function, electrolyte, beta2 microglobulin, C-reactive protein and immunoglobulin (M-protein) were detected. The involved spinal sites were examined by using magnetic resonance imaging (MRI) or computerized tomography (CT). 10 patients were staged according to International Stage System (ISS) and Duric-Salmon stage system. The clinical data of patients were analyzed. The results showed that among 10 cases of MM complicated by spinal infiltration, involved pectoral cord was observed in 7 cases, involved lumbar cord in 2 cases and sacral cord in 1 case. The treatment with operation and protocol containing cisplatin, ifosfamide etoposide, prednisone, and bortezomib in combination with other drugs indicated that the total remission rate was 80% (8/10), no serious adverse responses was observed. In conclusion, the patients with MM complicated by spinal infiltration must be diagnosed and treated as early as possible. Once paraplegia happened in patients, the therapeutic efficacy and prognosis would be very poor.

Bortezomib combined with other drugs for treating 60 cases of multiple myeloma / 中国实验血液学杂志

The aim of this study was to investigate the efficacy and safety of bortezomib-combined with dexamethasone, methylprednisolone and other drugs in the treatment of patients with multiple myeloma (MM). 60 MM patients including 19 de novo patients, out of them 14 patients received the treatment using regimen of bortezomib in combination with thalidomide (BT), 5 patients received bortezomib-methylprednisolone regimen (BMP). Out of 41 patients with refractory or relapsed myeloma 26 cases of MM received the treatment using regimen of bortezomib combined with methylpreamsolone (BMP), 6 cases received the treatment using regimen of bortezomib combined with cyclophosphamide, prednisone and thalidomide (BCPT), 5 cases received the treatment using regimen of bortezomib combined with cis-diaminodichloroplatimm, etoposide, cydophosphomide and dexamethasone (BDECD), 4 cases received the treatment using regimen of bortezomib combined with dexamethasone (BD). Each patient received treatment of 2-8 courses at least. Response was assessed according to the criteria of the Bladè. Adverse events were graded according to the common Toxicity Criteria, version 3.0 (NCI CTCAE, USA). The median follow-up from the start of bortezomib treatment was 9 months. The results showed that out of 19 newly diagnosed patients, 6 cares achieved CR, 6 cases achieved nearly CR, 5 cases achieved PR, 1 case achieved MR, resulting in an ORR of 94.7%. Out of 41 refractory or relapsed patients, 5 cases achieved CR, 10 cases got nearly CR, 14 cases were PR and 5 cases were MR, resulting in an ORR of 82.92%. The main toxicities were fatigue, gastrointestinal disorders, peripheral neuropathy, thrombocytopenia, herpes zoster, skin rash. All adverse events were diminished by using routine ways. In conclusion, bortezomib combined with or the drugs is a very effective regimen, its side effects are predictable and manageable.

Ex vivo expansion of CD34(+)CD59(+) cells from patients with paroxysmal nocturnal hemoglobinuria and their hematopoietic reconstitution capability in irradiated nude mice / 中国实验血液学杂志

This study was purposed to investigate the expansion and hematopoietic reconstitution capability of CD34(+)CD59(+) cells from patients with paroxysmal nocturnal hemoglobinuria (PNH) by using BALB/c nude mice so as to provide experimental basis for clinical anto-BMT or auto-PBHSCT in patients with PNH. CD34(+)CD59(+) cells were selected from the bone marrow mononuclear cells in normal persons and PNH patients by immunomagnetic positive double sorting and were engrafted sublethally irradiated BALB/c nude mice. The human CD45(+) cells in bone marrow, spleen and peripheral blood of recipient mice were detected by flow cytometry and DNA assay. The results showed that the CD34(+)CD59(+) cells in PNH patient group and normal person group could expanded ex vivo, but ex vivo expansion capability of CD34(+)CD59(+) cells in PNH patient group at day 7 seemed inferior to that in normal control. While CD34(+)CD59(+) cells of PNH patients and normal persons were transfused into recipient mice, the human CD45(+) cells could be detected in bone marrow, spleen and peripheral blood at 6 weeks after transfusion, but there was no statistical difference in counts of CD45 cells between 2 groups. It is concluded that CD34(+)CD59(+) cells from PNH patients may keep characteristics of normal hematopoietic stem cells, and possess ability to expand ex vivo and support hemopoiesis.

Nude mice intraperitoneally transfused with ex vivo expanded bone marrow CD34+ CD59+ cells from patients with paroxysmal nocturnal hemoglobinuria / 中国实验血液学杂志

Ex vivo expanded human bone marrow CD34(+)CD59(+) cells from patients with paroxysmal nocturnal hemoglobinuria (PNH) were transplanted into BALB/c mice in order to investigate their proliferation ability and reconstruction of hemopoiesis, and to lay the groundwork for clinical ABMT/APBSCT in PNH patients. CD34(+)CD59(+) cells were selected from the bone marrow mononuclear cells in PNH patients by using immunomagnetic positive double sorting. Sublethally irradiated BALB/c mice were transplanted with CD34(+)CD59(+) cells enriched from bone narrow of PNH patients. The results showed that human CD45(+) cells were detected in the bone marrow, spleen and peripheral blood of the nude mice by flow cytometry and DNA analysis at 6 weeks post-transplant. Blood routine indicators of nude mice were found to recover to some extent, but did not fully recover. It is concluded that ex vivo expanded bone marrow CD34(+)CD59(+) cells from patients with paroxysmal nocturnal hemoglobinuria could keep their biological characteristics and ability to reconstruct hemopoiesis in irradiated BALB/c mice.