OBJECTIVE: To retrospectively analyze the characteristics and influencing factors of COVID-19 infection in patients with multiple myeloma (MM) who underwent autologous hematopoietic stem cell transplantation (AHSCT). METHODS: The clinical data of MM patients who underwent AHSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 26, 2021 to December 26, 2022 were collected. The onset of COVID-19 infection, corresponding symptoms and laboratory tests were followed up in outpatient or by the means of telephone contact and online questionnaires. Related analysis was then performed. RESULTS: This study included 96 patients, and 72 cases among them were infected with COVID-19 while 24 cases were uninfected. Logistic regression analysis showed that vaccination did not significantly reduce the risk of COVID-19 infection, but patients who received two doses of the vaccine had a lower risk of developing moderate and severe disease than those who did not receive or received one dose (OR =0.06, P =0.029). Patients who received daratumumab before had a higher risk of COVID-19 infection (OR =5.78, P =0.039), while those with a history of immunomodulatory drugs (IMiDs) had the opposite effect (OR =0.31, P =0.028). The use of both drugs did not affect the severity of COVID-19 infection. CONCLUSION For MM patients undergoing AHSCT as first-line chemotherapy, COVID-19 vaccination does not significantly reduce the infection rate, but it plays a role in preventing moderate and severe cases. The application of antineoplastic drugs with different mechanisms has a certain impact on the susceptibility to the COVID-19, which should be considered comprehensively when creating treatment plans.
Humans ; Multiple Myeloma/complications* ; COVID-19/epidemiology* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Antibodies, Monoclonal

Multiple myeloma (MM) is a common hematologic malignancy that originates from precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Identifying its risk factors is crucial for early intervention. The etiology of MM is multifactorial, involving race, familial clustering, gender, age, obesity, cytogenetic abnormalities, and environmental exposures. Among these, cytogenetic abnormalities and modifiable factors play pivotal roles in MM pathogenesis and progression. 1) cytogenetic abnormalities. Primary abnormalities [e.g., hyperdiploidy, t(11;14), t(14;16)] emerge at the MGUS stage, while secondary abnormalities [e.g., 1q+, del(17p)] drive disease progression. The accumulation of 1q+ promotes clonal evolution, and del(17p) is associated with significantly reduced survival. 2) modifiable risk factors. Obesity promotes MM via the acetyl-CoA synthetase 2 (ACSS2)-interferon regulatory factor 4 (IRF4) pathway. Vitamin D deficiency weakens immune surveillance. Exposure to herbicides such as Agent Orange and glyphosate increases MGUS incidence. Insufficient UV exposure, by reducing vitamin D synthesis, elevates MM risk. Gut microbiota dysbiosis (enrichment of nitrogen-cycle bacteria and depletion of short-chain fatty acids producers) induces chromosomal instability through the ammonium ion-solute carrier family 12 member 22 (SLC12A2)-NEK2 axis. Therefore, risk-based screening among high-risk populations (e.g., those who are obese, elderly, or chemically exposed), along with early interventions targeting cytogenetic abnormalities [e.g., B cell lymphoma 2 (Bcl-2) inhibitors for t(11;14), ferroptosis inducers for t(4;14)] and modifiable factors (e.g., vitamin D supplementation, gut microbiota modulation), may effectively delay disease progression and improve prognosis.
Humans ; Multiple Myeloma/epidemiology* ; Risk Factors ; Obesity/complications* ; Chromosome Aberrations ; Monoclonal Gammopathy of Undetermined Significance/etiology* ; Gastrointestinal Microbiome ; Vitamin D Deficiency/complications* ; Precancerous Conditions/genetics*

BACKGROUND: There is limited data to comprehensively evaluate the epidemiological characteristics of multiple myeloma (MM) in China; therefore, this study determined the characteristics of the disease burden of MM at national and provincial levels in China. METHODS: The burden of MM, including incidence, mortality, prevalence, and disability-adjusted life years (DALYs), with a 95% uncertainty interval (UI), was determined in China following the general analytical strategy used in the Global Burden of Disease, Injuries, and Risk Factors Study 2019. The trends in the burden of MM from 1990 to 2019 were also evaluated. RESULTS: There were an estimated 347.45 thousand DALYs with an age-standardized DALY rate of 17.05 (95% UI, 12.31-20.77) per 100,000 in 2019. The estimated number of incident case and deaths of MM were 18,793 and 13,421, with age-standardized incidence and mortality rates of 0.93 (95% UI, 0.67-1.15) and 0.67 (95% UI, 0.50-0.82) per 100,000, respectively. The age-specific DALY rates per 100,000 increased to more than 10.00 in the 40 to 44 years age group reaching a peak (93.82) in the 70 to 74 years age group. Males had a higher burden than females, with approximately 1.5- to 2.0-fold sex difference in age-specific DALY rates in all age groups. From 1990 to 2019, the DALYs of MM increased 134%, from 148,479 in 1990 to 347,453 in 2019. CONCLUSION The burden of MM has doubled over the last three decades, which highlights the need to establish effective disease prevention and control strategies at both the national and provincial levels.
Humans ; Male ; Female ; Adult ; Aged ; Global Burden of Disease ; Quality-Adjusted Life Years ; Multiple Myeloma/epidemiology* ; Global Health ; Incidence ; Prevalence ; Risk Factors ; China/epidemiology*

OBJECTIVE: To explore and analyze the risk factors of herpes zoster in patients with multiple myeloma (MM) during the chemotherapy with bortezomib. METHODS: Clinical data of 85 MM patients treated with bontizomib from January 2015 to January 2019 were selected and divided into case group and control group accroding to the occurred of herpes zoster. The clinical characteristic, treatment outcome and related factor of herpes zoster were retrospective analyzed. RESULTS: Twenty of the 85 patients with MM treated with bortezomib developed herpes zoster occurred (23.5%). Single-factor analysis showed that age≥65 years, lymphocytopenia occurred before treatment, neutropenia occurred before treatment, ECOG score≥2, application of cyclophosphamide, absence of preventive antiviral therapy were associated with the genesis of herpes zoster (P＜0.05). Multivariate logistic regression analysis showed that lymphocytopenia occurred before treatment, the application of cyclophosphamide and the absence of preventive antiviral therapy were the independent risk factors for herpes zoster (P＜0.05). CONCLUSION The incidence of herpes zoster is high in the multiple myeloma patients treated with bortezomib. Lymphocytopenia occurred before treatment, the application of cyclophosphamide, and the absence of prophylactic antiviral therapy are the important risk factors for herpes zoster, for which the clinicians should attach great importance.
Boronic Acids ; Bortezomib ; Herpes Zoster/epidemiology* ; Humans ; Multiple Myeloma/drug therapy* ; Patients ; Pyrazines ; Retrospective Studies ; Risk Factors

OBJECTIVE: Patients with hematological malignancies frequently encounter spine-related symptoms, which are caused by disease itself or process of treatment. However, there is still lack of knowledge on their epidemiology and clinical courses. The purpose of this article is to review clinical presentations and surgical results for spinal involvement of hematologic malignancies. METHODS: From January 2011 to September 2014, 195 patients (98 males and 97 females) suffering from hematological malignancies combined with spinal problems were retrospectively analyzed for clinical and radiological characteristics and their clinical results. RESULTS: The most common diagnosis of hematological malignancy was multiple myeloma (96 patients, 49.7%), followed by chronic myeloid leukemia (30, 15.2%), acute myeloid leukemia (22, 11.2%), and lymphoma (15, 7.56%). The major presenting symptoms were mechanical axial pain (132, 67.7%) resulting from pathologic fractures, and followed by radiating pain (49, 25.1%). Progressive neurologic deficits were noted in 15 patients (7.7%), which revealed as cord compression by epidural mass or compressive myelopathy combined with pathologic fractures. Reconstructive surgery for neurologic compromise was done in 16 patients. Even though surgical intervention was useful for early paralysis (Frankel grade D or E), neurologic recovery was not satisfactory for the progressed paralysis (Frankel grade A or B). CONCLUSION: Hematological malignancies may cause various spinal problems related to disease progression or consequences of treatments. Conservative and palliative treatments are mainstay for these lesions. However, timely surgical interventions should be considered for the cases of pathologic fractures with progressive neurologic compromise.
Diagnosis ; Disease Progression ; Epidemiology ; Fractures, Spontaneous ; Hematologic Neoplasms* ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Lymphoma ; Male ; Multiple Myeloma ; Neurologic Manifestations ; Palliative Care ; Paralysis ; Retrospective Studies ; Spinal Cord Compression ; Spinal Cord Injuries ; Spine

Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration’s approval of newer agents, including carfilzomib, ixazomib, elotuzumab, and daratumumab. In concert with the technical advances in the cytogenetic and molecular diagnostics of MM, modifications of its diagnosis and staging system have been attempted for better risk stratification. The modified diagnostic criteria from the International Myeloma Working Group in 2014 enabled a strategy of more active treatment for some patients with smoldering MM, with an ultra-high risk of progression, and fine-tuned the definition of end-organ damage, known as CRAB (hypercalcemia, renal insufficiency, anemia, and bone lesions). Considering Korea’s trend of aging at an unprecedented rate, we can expect that the ASR of MM will maintain a gradual increase for many years to come; therefore, MM will be a cancer of critical importance from both medical and socioeconomic perspectives in Korea.
Aging ; Anemia ; Asian Continental Ancestry Group ; Cytogenetics ; Diagnosis ; Epidemiology ; Humans ; Incidence ; Korea ; Multiple Myeloma* ; Neoplasm Staging ; Pathology, Molecular ; Plasma Cells ; Renal Insufficiency

OBJECTIVETo investigate the clinical characteristics and prognosis of very young patients with multiple myeloma (MM).

METHODSWe retrospectively analyzed the clinical characteristics and outcome of 35 newly diagnosed MM patients 40 years old or younger during a period of 15 years and compared with published data from western countries.

RESULTSOur study demonstrated that these very young patients were more likely to be in advanced stage of International staging system, IgD isotype, hemoglobin<100 g/L, decreased platelets and deletion of 17p13. With a median follow-up of 17 months (1- 89 months), the median overall survival (OS) of this cohort was 33 months and progression-free survival (PFS) was 13 months, moreover 8 of 17 deaths occurred in the first year after diagnosis. In the univariate analysis, extramedullary infiltration, del (17p13）and renal impairment were associated with reduced PFS (P=0.031, P=0.015, P=000, respectively), while the last two factors also predicted inferior OS (P=0.015, P=0.001), but multivariate analysis showed that only renal impairment independently associated with inferior survival in COX model（PFS: HR=3.953, 95% CI 1.263-12.371, P=0.018; OS: HR=5.769, 95% CI 1.602- 20.771, P=0.007).

CONCLUSIONOur research showed for the first time that the clinical characteristics and survival of MM patients ≤ 40 years old in China were different from that in western countries. The special attention should be paid to the patients with their diagnosis and treatment.

Adult ; China ; epidemiology ; Chromosome Deletion ; Disease-Free Survival ; Humans ; Multiple Myeloma ; diagnosis ; epidemiology ; Prognosis ; Retrospective Studies

Many advances in the treatment of multiple myeloma have been made due to the use of transplantation and the introduction of novel agents including thalidomide, lenalidomide, and bortezomib. The first step is recognizing the symptoms and starting prompt treatment. Different strategies should be selected for young and elderly subjects. Young patients are commonly eligible for transplantation, which is now considered the standard approach for this setting, and various inductions therapies containing novel agents are available before transplantation. Elderly patients are usually not eligible for transplantation, and gentler approaches with new drugs combinations are used for their treatment.
Age Factors ; Antineoplastic Agents/therapeutic use ; Boronic Acids/therapeutic use ; Humans ; Immunologic Factors/therapeutic use ; Multiple Myeloma/diagnosis/epidemiology/*therapy ; Prognosis ; Pyrazines/therapeutic use ; Stem Cell Transplantation ; Thalidomide/analogs & derivatives/therapeutic use

BACKGROUNDAllogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma.

METHODSThe conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea (40 mg/kg) was administered twice on day-10 and cytarabine (2 g/m(2)) was given on day-9, busulfan was administered orally in four divided doses daily for 3 days (days-8 to -6). The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days-5 and -4 (1.8 g/m(2)), and with semustine (Me-CCNU) 250 mg/m(2) on day -3.

RESULTSChimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease (GVHD, 36.4%; 95% CI: 13.9% - 38.6%). Two patients (18.2%) developed grade I acute GVHD (95% CI: 10.9% - 35.9%) and grade II acute GVHD occurred in one patient (9.1%; 95% CI: 8.4% - 32.3%). Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% (95% CI: 11.7% - 36.7%), among them one died of severe grade IV GVHD and one developed multiorgan failure on day +170; the treatment-related mortality was 22.0% (95% CI: 10.3% - 34.1%). The overall 4-year survival rate was 67.8% (95% CI: 16.3% - 46.7%). The estimated 4-year progression-free survival rate was 58.5% (95% CI: 13.7% - 41.8%). The 4-year complete remission was 72.7% (95% CI: 27.8% - 49.6%). One patient relapsed after 4 months and achived the complete remission after receiving the donor lymphocyte infusion.

CONCLUSIONSModified conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells + bone marrow cells transplantation result in a low incidence of severe GVHD with a relatively low treatment-related mortality, high complete remission rates and a long-term survival.

Adult ; Busulfan ; administration & dosage ; Cyclophosphamide ; administration & dosage ; Female ; Graft vs Host Disease ; epidemiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; mortality ; therapy ; Transplantation Conditioning ; Transplantation, Homologous

Multiple myeloma is a hematologic neoplasm with a unique and characteristic manifestation. This condition is responsible for 10% of hematologic malignancies, and thus represents 1% of all cases of cancer in the US. In Korea, unlike in Western society, myeloma has classically been relatively rare, due in part to racial differences. However, the incidence of this disease in Korea has increased steadily over the last 25 years. During this period, both the incidence of and mortality due to myeloma increased by up to 30-fold. Currently, incidence rate and mortality rate exceed 1.0/100,000. Possible reasons for this increase include better detection, as well as an actual increase, probably attributable to contributing factors, including pollution, exposure to chemicals, and socioeconomic change, all of which are related to rapid industrialization. Aging is another important factor contributing to this perceived increase. With the advent of targeted therapy, Korean myeloma study group was organized under the auspice of Korean society of hematology. In addition, Korean myeloma registry was established recently. In this study, epidemiological changes in the incidence and mortality of multiple myeloma in Korea are assessed and compared with the situations of the US and Japan. This article also claims the need for multicenter clinical trials as well as activation of basic researches in myeloma.
Aging ; Epidemiologic Studies ; Epidemiology ; Hematologic Neoplasms ; Hematology ; Incidence ; Japan ; Korea* ; Mortality ; Multiple Myeloma* ; Prevalence ; Industrial Development