Outcome of patients with IgD and IgM multiple myeloma undergoing autologous hematopoietic stem cell transplantation: a retrospective CIBMTR study

IntroductionImmunoglobulin D (IgD) and IgM multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% and 0.5% of cases, respectively. Limited information is available regarding the prognosis of these isotypes, but they have been considered to have a more aggressive course than the more common immunoglobulin G (IgG) and IgA isotypes. In particular, the outcome after autologous hematopoietic stem cell transplantation (auto-HCT) has not been well defined.Patients and MethodsUsing the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 36 patients with IgD and 11 patients with IgM myeloma among 3578 myeloma patients who received intensive therapy and auto-HCT over a 10-year period.ResultsThe progression-free and overall survival probabilities at 3 years were 38% (95% CI, 21%-56%) and 69% (95% CI, 51%-84%) for IgD myeloma, and 47% (95% CI, 17%-78%) and 68% (95% CI, 36%-93%), respectively, for IgM disease. Although formal statistical analysis was limited by the small sample size, these results were comparable to those for IgG and IgA patients autografted during the same time period. Transplantation-related mortality and disease relapse/progression of myeloma were also similar for all isotypes.ConclusionThis analysis demonstrates comparable outcomes in all immunoglobulin isotypes. Therefore, auto-HCT should be offered to eligible patients with IgD and IgM myeloma.     

Immunoglobulin D multiple myeloma: response to therapy,survival, and prognostic factors in 75 patients

BackgroundTo analyze the clinical features, outcomes including efficacy of treatment, and prognostic factors of patients with immunoglobulin D multiple myeloma (IgD MM).Design and methodsSeventy-five patients diagnosed with IgD MM were selected from the Korean Myeloma Registry database (www.myeloma.or.kr).ResultsMedian age was 57 years and the main presenting features were bone pain (77%). Renal function impairment and hypercalcemia were present in 40 (53%) and 20 (27%) patients. Sixty-seven patients (89%) had lambda light chains. Forty-eight patients (64%) were of stage III by International Staging System. Twenty-six patients (53%) had chromosomal abnormalities mostly by conventional cytogenetics. Thirty-nine patients (54%) were treated with vincristine, adriamycin, and dexamethasone chemotherapy; the overall response rate (ORR) of 56%. Sixteen patients (22%) received first-line chemotherapy including new drugs (bortezomib or thalidomide), with an ORR of 81%. At a median follow-up time of 28.6 months, median overall survival (OS) was 18.5 months. Age, extramedullary plasmacytoma, del(13) or hypoploidy, serum β₂ microglobulin level, and platelet count were significant prognostic factors for OS.ConclusionsIgD MM is an aggressive disease that is usually detected at an advanced stage. Despite a positive initial response, survival after relapse was dismal. Intensive treatment strategies before and following stem cell transplantation may improve outcomes in younger patients.     

The prolonged activated partial thromboplastin time at diagnosis indicates less favorable prognosis in IgA myeloma

BACKGROUND: The impact of coagulopathy on survival of patients with myeloma has not been studied in detail. We aimed to assess the correlation between activated partial thromboplastin time/prothrombin time at diagnosis and overall survival in myeloma patients. METHODS: Data including activated partial thromboplastin time and prothrombin time obtained before treatment and at the time of diagnosis of multiple myeloma (excluding monoclonal gammopathy of undetermined significance, POEMS syndrome, IgM myeloma and myeloma with amyloidosis) collected from 222 patients were analyzed. RESULTS: Twenty-one patients (9.5%) had prolonged activated partial thromboplastin time (nine with prolonged a activated partial thromboplastin time alone, 12 with both prolonged activated partial thromboplastin time and prothrombin time) and 10 (4.5%) had prolonged prothrombin time alone. Coagulopathy occurred only in patients with IgA and IgG myeloma but not light-chain disease. Prolonged activated partial thromboplastin time was an independent prognostic factor in IgA and IgG myeloma (median survival = 12.7 months, P = 0.004), while prolonged prothrombin time alone had no impact on survival. Subgroup analysis revealed that prolonged activated partial thromboplastin time indicated less favorable survival in IgA myeloma (P = 0.001), but not the IgG myeloma (P = 0.341). This observation still holds true in IgA myeloma with Durie-Salmon stage II or III (P = 0.002). CONCLUSIONS: The presence of prolonged activated partial thromboplastin time at diagnosis is a prognostic factor indicating poor outcome in the IgA myeloma.     

Promoter hypermethylation of the MEG3 (DLK1/MEG3) imprinted gene in multiple myeloma

BackgroundMethylation represents the most studied epigenetic modification and results in the silencing of genes involved in various processes such as differentiation and cell-cycle regulation. MEG3 represents an imprinted gene maternally expressed in humans that encodes a nontranslated product. In this survey, we studied the methylation status of the specific gene in multiple myeloma (MM).Patients and MethodsTwenty-one patients with MM (17 with immunoglobulin [Ig] G, 3 with IgA, and 1 with IgM) were evaluated using methylation-specific polymerase chain reaction (after DNA bisulphite modification).ResultsPromoter hypermethylation was observed in 12 (57.14%) bone marrow samples and in 9 of 14 (64.28%) available peripheral blood samples. A correlation with disease stage was also observed and also with the disease subtype (IgG, 64.7%; IgA, 0; IgM, 100%).ConclusionWe conclude that promoter hypermethylation of the differentially methylated region of the MEG3 imprinted gene is observed in patients with MM.     

Spinal lesions in multiple myeloma: Primary bone tumors with distinct prognostic factors

PurposeAlthough prognostic factors of spinal multiple myeloma (MM) seem to differ from those of other spine metastases (SpM), the data in the literature remains scarce.MethodsA prospective population of 361 patients treated for spine MM lesions between January 2014 and 2017.ResultsOS for our series was 59.6 months (SD 6.0 months; CI 95%: 47.7–71.3). Cox multivariate proportional-hazards analysis showed that bone marrow transplant [HR: 0.390, 95% CI 0.264–0.577; p < 0.0001] and light-chain isotype [HR: 0.748, 95% CI 0.318–1.759; p = 0.005] were independent predictors of longer survival. In contrast, age >80 years [HR: 2.7, 95% CI 1.6–4.3; p < 0.0001], ISS III [HR: 2.510, 95% CI 2.01–3.124; p = 0.001], IgA isotype [HR: 1.475, 95% CI 1.031–2.11; p = 0.034] and IgD/M isotype [HR: 2.753, 95% CI 1.230–6.130; p = 0.013] were independent poor prognostic factors. However, ECOG (p = 0.486), spine surgery (p = 0.391), spine radiotherapy (p = 0.260), epidural involvement (p = 0.259), the number of vertebra lesions (p = 0.222), and synchronous/metachronous timeline (p = 0.412) were not significantly associated with improved OS.ConclusionsSpinal involvement in the context of MM does not influence OS. The main prognostic factors to consider before spinal surgery are the characteristics of the primary MM disease (ISS score, IgG isotype and systemic treatment).     

Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia

Nonsecretory myeloma, which accounts for 1% to 5% of all myelomas, is characterized by the absence of detectable M-protein in serum and urine. The presenting features of nonsecretory myeloma are similar to those in patients with a detectable M-protein, except for the absence of renal function impairment. The response to therapy and survival of patients with nonsecretory myeloma are similar to those of patients with measurable M-protein. Immunoglobulin D myeloma represents 2% of all myelomas. Patients with IgD myeloma usually present with a small band or no evident M-spike on serum electrophoresis and heavy light-chain proteinuria. Thus, IgD myeloma can be considered a variant of Bence Jones myeloma; the presence of the IgD M-protein and the predominance of the lambda light chain are the only distinctive features. The median survival of patients with IgD myeloma is almost 2 years, with one fifth of them surviving for more than 5 years. Plasma cell leukemia is also a rare form of plasma cell dyscrasia (2% to 4% of all myelomas). The primary form accounts for 60% of the cases. In primary PCL, the constellation of adverse biologic prognostic factors in patients with advanced aggressive myeloma is already present at diagnosis. In fact, primary PCL has a more aggressive clinical presentation than MM, with a higher frequency of extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, and renal failure. Treatment with a single alkylating agent plus prednisone is not appropriate. Combination chemotherapy with VAD, cyclophosphamide and etoposide, or VCMP/VBAP is a better initial option. Given the poor prognosis of primary PCL, intensification with high-dose therapy followed by stem cell rescue should be offered to affected patients.     

Microsatellite Instability Is a Common Finding in Multiple Myeloma

PurposeMicrosatellite instability (MSI) occurs as a result of sliding in the DNA sequences from shortening or elongation of the repeat zones of DNA during replication. Such abnormalities can normally be corrected by the enzymes coded by the DNA mismatch repair (MMR) genes. Therefore, detection of MSI is considered to be a sign of disorder of the MMR genes and is interpreted as a replication error phenotype.Patients and MethodsWe evaluated the MSI in 5 different loci in the 14q32 region of immunoglobulin heavy chain IgH gene in 26 newly diagnosed patients with multiple myeloma (MM).ResultsFifty-four percent of the patients disclosed MSI and at least 1 locus but no significant association of MSI was found between different clinical stages and the MM subtype. MSI was not found in 5 light-chain myeloma patients.ConclusionAlthough our case number is small, probably the genomic instability in heavy-chain MM may be a common finding and probably plays a critical role in the MM pathogenesis.     

Abnormal heavy/light chain ratio after treatment is associated with shorter survival in patients with IgA myeloma

Immunoglobulin (Ig) heavy/light chain (HLC) assays enable the separate quantification of the different light chain types of each Ig class. We retrospectively analyzed the correlation of heavy/light chain ratio (HLCR) with clinical status and its impact on outcome in 120 patients with multiple myeloma (MM). Abnormal HLCR was seen more frequently in patients with poorer myeloma response, and it appeared to be more sensitive for detecting clonality in IgA myeloma compared to IgG myeloma after treatment. Among the 85 patients who achieved ≥VGPR, the patients remained HLCR abnormal were showed significantly shorter overall survival (OS) compared to those achieving a normal HLCR (not reached vs 55.5 months, P = 0.032). This correlation was seen in IgA myeloma patients (not reached vs 30.1 months, P = 0.014), but not in IgG myeloma patients when patients were analyzed separately. Univariate and multivariate analysis of factors that may affect survival identified abnormal HLCR at the best response as the only independent risk factor (hazard ratio, 4.7; 95% confidence interval, 1.4 – 15.26; P = 0.012) for shorter OS in this subset of patients. This study highlighted the HLC assay as a prognostic predictor in patients with IgA myeloma.     

Cytogenetic Features and Clinical Outcomes of Patients With Non-secretory Multiple Myeloma in the Era of Novel Agent Induction Therapy

BackgroundNon-secretory multiple myeloma (NSMM) is a rare subtype of multiple myeloma (MM) characterized by the absence of monoclonal protein in the serum and/or urine. We look at the clinical and cytogenetic features of NSMM in this study.Patients and MethodsThis study evaluates a cohort of 30 patients with newly diagnosed NSMM seen at the Mayo Clinic, Rochester, MN, between 2008 and 2018 and treated with novel agent induction therapies. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.ResultsThese patients with NSMM appear to have a large disease burden at diagnosis with a median bone marrow plasma cell percentage of 70% and more than one-half of all patients having Multiple Myeloma International Staging System Stage III disease. There was a higher preponderance for t(11;14) primary cytogenetic abnormality in this NSMM cohort, accounting for more than 50% of the cohort. Finally, the overall survival of this cohort appears to be slightly worse than a matched-control group of newly diagnosed patients with MM with secretory disease.ConclusionsFuture multi-institution studies confirming these above findings on this rare entity are warranted.     

多发性骨髓瘤发生初次化疗近期死亡的临床特点及危险因素分析

  目的  探讨多发性骨髓瘤（MM）发生初次化疗近期死亡患者的临床特征和危险因素。  方法  对2004年1月~2012年10月期间初治的111例MM患者的临床资料进行回顾性分析。  结果  MM患者确诊后6个月内死亡15例，其中10例于第1个化疗用药期或间歇期死亡，占全部化疗例数的9%。10例初次化疗近期死亡患者，中位生存时间为5天。其中，轻链型7例，IgG型3例；死于严重感染及并发症8例。单因素分析显示，IFE分型为轻链型、化疗前低血小板、低白细胞、低中性粒细胞水平、ECOG评分升高、血清肌酐水平升高与第1个周期化疗近期死亡风险增加有关。多因素回归分析显示，M蛋白为轻链型（P=0.003，OR= 12.976，95%CI:2.328~72.322）、化疗前血小板低水平（P=0.034，OR=6.141，95%CI:1.152~32.739）及中性粒细胞水平（P=0.003，OR=13.639，95%CI:2.398~77.564）是发生初次化疗近期死亡的独立危险因素。  结论  初始化疗对于相当部分MM患者具有特殊的致命风险。严重感染及其并发症是直接导致化疗近期死亡的主要原因。影响MM总体生存的预后因素并不能完全决定初次化疗的死亡风险。轻链型骨髓瘤、化疗前低血小板及低中性粒细胞水平是发生初次化疗近期死亡的独立危险因素。      

Bortezomib and Dexamethasone Therapy for Newly Diagnosed Patients With Multiple Myeloma Complicated by Renal Impairment

BackgroundRenal impairment is a common complication of multiple myeloma (MM) and is related to shorter overall survival and increased rates of early death. Bortezomib is a new agent for the treatment of patients with myeloma, with high response rates and controllable side effects. In this study, we will evaluate the efficacy and safety of bortezomib and dexamethasone in patients with newly diagnosed MM complicated by renal impairment.Patients and MethodsThis is a prospective study of the general characteristics, reversibility of renal impairment, response of myeloma, and side effects of 18 consecutive newly diagnosed patients with MM and renal impairment who received ≥ 2 cycles of bortezomib and dexamethasone.ResultsOf 18 patients newly diagnosed with MM, the median age was 60 years, and the median serum creatinine was 5.3 mg/dL. Patients received a median of 4 cycles of bortezomib and dexamethasone. Reversal of renal impairment was documented in 38.9% of the patients, and the median time to reversal was 16 days. Moreover, 33.3% of the patients achieved renal response (a 50% decrease in serum creatinine). The overall response rate of MM was 83.3%, including a 33.3% complete response (CR) rate, a 16.7% near-CR rate, a 16.7% very good partial response (PR) rate, and a 16.7% PR rate. Grade 3/4 adverse events consisted of infection (n = 3), peripheral neuropathy (n = 3), and ileus (n = 1). After a median follow-up of 15.7 months, the median progression-free survival for all patients was 12.6 months.ConclusionBortezomib plus dexamethasone is a safe and effective regimen for newly diagnosed patients with MM complicated by renal impairment.     

Predictors of Lenalidomide Refractory Relapse Timing With Newly Diagnosed Multiple Myeloma: A FIRST Trial Subanalysis

Introduction/BackgroundMultiple myeloma (MM) is considered an incurable cancer. Patients with newly diagnosed MM (NDMM) are at risk for relapse within 1 year of frontline therapy. The immunomodulatory agent lenalidomide combined with dexamethasone (Rd) may be used as treatment for NDMM or relapsed MM, including in patients ineligible for autologous stem cell transplant.PatientsThis subanalysis of the phase III FIRST trial characterized patients with transplant-ineligible NDMM who experienced relapse while receiving Rd therapy by relapse timing (early [<12 months] versus late [≥12 months]) and type (CRAB vs. non-CRAB).MethodsThe Kaplan-Meier product limit method was used to estimate time-to-event endpoints, including progression-free survival (PFS) and overall survival (OS). Factors associated with the odds of late relapse were identified by logistic regression with univariate and multivariate analyses using a binary outcome (relapse at <12 vs. ≥12 months) in patient-, disease-, and treatment-specific baseline variables.ResultsPatients with early refractory relapse had functionally high-risk disease and inferior outcomes. In patients with early relapse versus those with late relapse, median OS (95% CI) was 26.8 months (21.9-32.8) versus 63.9 months (57.0-78.0), median OS from disease progression to death was 19.9 months (16.0-25.5) versus 36.4 months (27.9-47.0), and median PFS from randomization to second progression was 19.1 months (17.3-22.5) versus 42.1 months (37.4-44.9). Lactate dehydrogenase, baseline β2 microglobulin, and myeloma subtype were shown to predict time to relapse.ConclusionsClinicians could use these factors to consider more aggressive treatment regimens for those at highest risk of early relapse.     

多发性骨髓瘤患者M蛋白标记的临床意义

目的:探讨多发性骨髓瘤（multiple myeloma,MM）患者血清蛋白电泳M蛋白标记的临床意义,观察其定量水平监测疾病进展和评估治疗药物的疗效。方法:对169例患者血清蛋白电泳的M蛋白波峰进行柱状法标记,通过免疫固定电泳(IFE)确诊其免疫分型,同时进行血清总蛋白（TP）、白蛋白(ALB)含量检测。连续追踪25例初诊诊断为MM患者的血清蛋白电泳,将M蛋白波峰标记得到M 蛋白百分比,换算M 蛋白浓度。换算公式:M 蛋白浓度（g/L）=TP浓度（g/L）×M蛋白百分比（%）,将计算结果进行对比。结果:在169例患者中,血清蛋白电泳β区见M蛋白波峰49例（29.0%）、γ区见M蛋白波峰120例（71.0%）,经过IFE分型:κ型IgG 型48例(28.4%),λ型IgG型43例(25.4%);κ型IgA型14例(8.3%),λ型IgA型16例(9.5%);κ型IgM 11例(6.5%),λ型IgM 3例(1.8%);κ型IgD型 2例(1.2%),λ型IgD型6例(3.6%); 游离κ轻链型2例(1.2%),游离λ轻链型8例(4.7%);双克隆型 1例(0.6%);未见单克隆条带15例(8.9%)。随访和监测25例MM患者化疗疗效评估:化疗后较化疗前白蛋白明显升高;其中β区M蛋白4例,β球蛋白及M蛋白浓度明显降低,差异均有统计学意义（P＜0.05）;γ区M蛋白21例,γ球蛋白及M蛋白显著降低（P＜0.05、P＜0.01）,其中M蛋白持续存在的MM患者,第1次评估血清TP含量和M 蛋白浓度明显下降、ALB含量明显升高,第2次评估TP、ALB含量在正常参考值区间,趋于平稳,M 蛋白浓度逐渐下降,可至消失。结论:血清蛋白电泳M蛋白的标记是诊断MM、巨球蛋白血症、淀粉样变等浆细胞病的依据,可作为标志物对其定量,更好的为监测疾病进展和评估治疗药物的疗效提供指导。     

A descriptive study of plasma cell dyscrasias in Egyptian population

BackgroundPlasma cell dyscrasias (PCDs) refer to a spectrum of disorders characterized by the monoclonal proliferation of lymphoplasmacytic cells in the bone marrow and, sometimes, tissue deposition of monoclonal immunoglobulins or their components. These disorders include multiple myeloma (MM) and Waldenström’s macroglobulinemia, as well as rare conditions such as light-chain deposition disease (LCDD) and heavy-chain diseases (HCDs). The worldwide annual incidence of MM is estimated at 86,000, which is approximately 0.8% of all new cancer cases.PurposeOur retrospective study aims to highlight the immunologic and epidemiological features of PCDs mainly MM in Egyptian patients and compare our results with those of other populations.MethodsTwo hundred seventeen Egyptian patients with PCD were enrolled in the study. Serum, urine protein electrophoresis and immunofixation were used to demonstrate M protein.ResultsOne hundred thirty-eight patients (63.6%) had IgG monoclonal band, 38 patients (17.5%) had IgA, 12 patients (5.5%) had Waldenström’s macroglobulinemia (IgM monoclonal band) and 29 patients (13.4%) were light chain myeloma. One hundred fifty-one (70%) were Kappa chain positive and 66 patients (30%) were lumbda positive. Conventional cytogenetics was available for 40 patients; of them12 patients (30%) showed 13q-. Mean OS was 37.5 months (1–84 months). Survival analysis was statistically insignificant according to age, sex and ISS or type of treatment (P value > 0.05).ConclusionLong term follow up is required to further define the role of different therapeutic lines of treatment including ASCT in the various stages of PCD based on OS data.     

Epidemiology of the M-component immunoglobulin types of multiple myeloma

The purpose of this population-based case-control study was to learn whether risk factors differ for the individual immunoglobulin types of multiple myeloma. In particular, we sought to determine whether IgA and IgG myeloma were related to a history of exposure to reported IgA- and IgG-stimulating conditions, respectively, or to a history of selected occupational and physicochemical exposures. The M-component immunoglobulin type was determined from immunoelectrophoresis as reported in medical records, and exposure status was obtained through in-person interviews. IgG (56 percent) and IgA (22 percent) M-components predominated. For 17 percent of cases, no peak was found on immunoelectrophoresis; they were presumed to have light-chain myeloma. Persons with these three types of myeloma did not differ with respect to distributions of age or race, but a somewhat higher proportion of light-chain cases were women (58 percent cf 45 percent of all other cases). Detailed analysis of the IgA and IgG subtypes provided little evidence that they differ with respect to prior immune stimulation or employment in several specific jobs. IgA myeloma, but not IgG myeloma, was associated modestly with a history of exposure to chest and dental X-rays. Our study provides little evidence that IgA and IgG myeloma differ with respect to the risk factors examined.Ms Herrinton and Drs Koepsell, Weiss, and Daling are with the Department of Epidemiology, University of Washington, Seattle, WA, USA, and the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Dr Demers is with the Department of Environmental Health, University of Washington, Seattle, WA, USA. Dr Taylor is with Group Health Cooperative of Puget Sound, Seattle, WA, USA. Dr Lyon is with the School of Medicine, University of Utah, Salt Lake City, UT, USA. Dr Swanson is with the Cancer Center, Michigan State University, East Lansing, MI, USA. Dr Greenberg is with the School of Public Health, Emory University, Atlanta, GA, USA. Address correspondence to Ms Lisa Herrinton, Fred Hutchinson Cancer Research Center, 1124 Columbia MP-381, Seattle, WA 98104, USA. The project was supported by grants CA23350, CA39779, and CA09168 from the US National Cancer Institute.     

IgD Subtype But Not IgM or Non-Secretory Is a Prognostic Marker for Poor Survival Following Autologous Hematopoietic Cell Transplantation in Multiple Myeloma. Results From the EBMT CALM (Collaboration to Collect Autologous Transplant Outcomes in Lymphomas and Myeloma) Study

BackgroundThe Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study has provided an opportunity to evaluate the real-world outcomes of patients with myeloma. The aim of this study was to compare the outcome according to the different subtypes of myeloma using CALM data.PatientsThis study compared overall survival (OS), progression-free survival (PFS), and complete remission (CR) and the impact of novel versus non-novel drug containing induction regimens prior to autologous hematopoietic cell transplantation (HCT) of 2802 patients with “usual” and “rare” myelomas.ResultsOur data suggest that IgM and non-secretory myeloma have superior PFS and OS compared with IgD myeloma and outcomes comparable to those for usual myeloma. Patients who received novel agent induction had higher rates of CR prior to transplant. Non-novel induction regimens were associated with inferior PFS but no difference in OS. Although not the primary focus of this study, we show that poor mobilization status is associated with reduced PFS and OS, but these differences disappear in multivariate analysis suggesting that poor mobilization status is a surrogate for other indicators of poor prognosis.ConclusionWe confirm that IgD myeloma is associated with the worst prognosis and inferior outcomes compared with the other isotypes.     

Low Grade Fibromyxoid Sarcomas and Multiple Myeloma in the Same Patient: One Case Report and Literature Review

Introduction Multiple myeloma (MM) is a neoplastic plasma cell dyscrasia char-acterized by anemia; a monoclonal protein(M-protein) in the serum and/or urine; abnormal bone radiographs and bone pain;hypercal-cemia; and renal insuf.ciency or failure.According to the results of immunoelectrophoresis, patients are separated to Ig type (IgG, IgA, IgD, IgE and IgM); light chain; nonsecretory[1].     

Induction Treatment With Cyclophosphamide,Thalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: A Phase II Study

Background:Thalidomide has alternative mechanisms of action; it can be combined with dexamethasone or alkylating agents for the treatment of multiple myeloma (MM); however, the optimal doses and appropriate intervals of thalidomide continue to be debated.Patients and Methods:We assessed the clinical efficacy and toxicity of thalidomide in patients with newly diagnosed MM; 68 patients were treated with pulsed cyclophosphamide, thalidomide, and dexamethasone (CTD) chemotherapy for induction treatment.Results:After a median of 28 months' follow-up, the overall response rate was 79.4%, with a 42.6% complete response (CR) or very good partial response (VGPR). Patients with cytogenetically high-risk disease had poor CR/VGPR rates (27.3%) at a median of 11.5 months of time to progression (TTP) compared with patients with standard-risk disease who achieved CR/VGPR rates (50%) at a median of 20.3 months of TTP. The major adverse events included peripheral sensory neuropathy (14.3%), infection (10.2%), and thromboembolic complications (5.9%). Thirty-two patients who achieved more than a PR proceeded to peripheral blood stem cell collection with a median number of 5.0 × 10⁶ CD34⁺ cells/kg collected.Conclusion:CTD resulted in a favorable response with tolerable toxicity in patients with MM and did not affect the yield of the stem cell collection.     

Multiple myeloma-induced hyperammonemic encephalopathy: An entity associated with high in-patient mortality

Hyperammonemia attributed to multiple myeloma (MM) has been rarely reported. We present 6 patients from our institution and 34 from the literature with MM-induced hyperammonemic encephalopathy. The median age was 67 years with male:female ratio of 1.8:1. The median ammonia level was 114 umol/L. IgG and IgA MM was seen in 40% and 35% of cases, respectively. The in-patient mortality was 48%. The in-patient mortality was 31% in patients who received MM-directed therapy and 100% in those who did not received MM-directed therapy. Hyperammonemic encephalopathy is a rare complication in MM and is associated with high in-patient mortality.     

Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis

The aim of this study was to understand the clinical features and treatment outcome of Chinese patients with multiple myeloma (MM). This retrospective study enrolled 940 newly diagnosed inpatients (median age, 59 years; immunoglobulin (Ig)D isotype, 6.5%) with complete follow-up data at three centers. In all, 85.8% of patients were of Durie-Salmon stage III and 48.3% were of International Staging System (ISS) stage III at diagnosis. Also, 9.6% of patients had extramedullary plasmacytoma. Compared with IgG, IgD-type patients were diagnosed at a younger age, and more patients were of ISS stage III, with hypercalcemia, elevated levels of lactate dehydrogenase, hyperuricemia, renal dysfunction and 1q21 amplification (P=0.03). The overall survival (OS) benefit was more prominent in IgG than in IgD when patients received bortezomib; however, they showed no significant difference when they received older therapies such as melphalan combined with prednisone or vincristine combined with adriamycin and dexamethasone. Fluorescence in situ hybridization (FISH) results showed that 17.6% had 17p13 deletion. Conventional cytogenetics revealed that 13.3% were hypodiploid and those cases had the worst survival, but hyperdiploid cases (9.3%) did not show any survival benefit compared with those with a normal karyotype (77.4%). Median OS and progression-free survival for all patients were 54 and 26 months, respectively. Significant factors for survival by multivariate analysis were gender, ISS stage, number of FISH abnormalities and extramedullary disease. MM in mainland China presents with different features, with patients being of younger age and having higher risk and more survival benefit in IgG patients receiving bortezomib.