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Hematopoietic Stem Cell Transplantation for Multiple Myeloma. Koniarczyk Heather L,Ferraro Christina,Miceli Teresa Seminars in oncology nursing OBJECTIVE:To provide an overview of the hematopoietic stem cell transplantation (HSCT) process specific to patients with multiple myeloma (MM) and their caregivers. DATA SOURCES:Research studies, book chapters, websites, expert knowledge, and journal articles. CONCLUSION:Although not curative, autologous HSCT is an important, manageable treatment modality, and continues to be a standard of care in MM for those patients who are eligible. IMPLICATIONS FOR NURSING PRACTICE:Although an area of specialty practice, an understanding of the HSCT process is important to broaden the knowledge of all nurses who care for patients with MM. 10.1016/j.soncn.2017.05.004
[Clinical Analysis on the Therapeutic Efficacy of Autologous Hematopoietic Stem Cell Transplantation in 56 Multiple Myeloma Patients]. Wang Chao-Yu,Xia Bing,Ning Qiao-Yang,Tian Chen,Zhao Hai-Feng,Yang Hong-Liang,Li Meng-Zhen,Zhao Zhi-Gang,Wang Xiao-Fang,Wang Ya-Fei,Yu Yong,Zhang Yi-Zhuo Zhongguo shi yan xue ye xue za zhi OBJECTIVE:To evaluate the therapeutic efficacy and prognosis of autologous stem Hematopoietic cell transplantation (auto-HSCT) in multiple myeloma (MM) patients. METHODS:A retrospective study was conducted for 56 patients diagnosed with MM and then received auto-HSCT in our hospital from December 2008 to September 2016. RESULTS:All the patients successfully underwent hematopoietic reconstruction without transplantation-related mortality (TRM). The complete response (CR) rate of all the patients after induction chemotherapy was 23.2% (13/56), while the CR rate of these patients with auto-HSCT increased to 78.6% (44/56) (P<0.01). The CR plus VGPR (very good partial response) rates of these 56 patients after induction chemotherapy and auto-HSCT were 53.6%(30/56)and 94.6%(53/56) respectively (P<0.01). The median progression-free survival (PFS) time and median overall survival (OS) time were 37 and 71 months, respectively. The median PFS time in the patients with induction therapy containing bortezomib was 37 months, however, the median OS time did not reach to 71 months; the median PFS (P<0.01) and the median OS (P<0.01) in the patients with the induction chemotherapy without bortezomib was 27 and 51 months, respectively. Univariate analysis demonstrated that the patients maintained CR or VGPR after auto-HSCT or with less than 6 cycles of induction chemotherapy significantly correlated with PFS (P<0.01). CONCLUSION:auto-HSCT can further increase the CR rate, prolong PFS and OS time. Sequential auto-HSCT after bortezomib-based therapy is the first line therapy for the transplant-eligible MM patients. Maintenance treatment is beneficial to the sustained CR+VGPR patients after auto-HSCT. 10.7534/j.issn.1009-2137.2018.05.023
Comparison between autologous and allogeneic stem cell transplantation as salvage therapy for multiple myeloma relapsing/progressing after autologous stem cell transplantation. Ikeda Takashi,Mori Keita,Kawamura Koji,Mori Takehiko,Hagiwara Shotaro,Ueda Yasunori,Kahata Kaoru,Uchida Naoyuki,Tsukada Nobuhiro,Murakami Satoshi,Yamamoto Masahide,Takahashi Tsutomu,Ichinohe Tatsuo,Onizuka Makoto,Atsuta Yoshiko,Kanda Yoshinobu,Okamoto Shinichiro,Sunami Kazutaka,Takamatsu Hiroyuki Hematological oncology Allogeneic stem cell transplantation (allo-SCT) offers a clinical option to young patients with multiple myeloma (MM) relapsing/progressing after autologous SCT (ASCT); however, this claim remains debatable. Thus, in this retrospective study, we analyzed 526 patients with MM who underwent SCT for MM relapsing/progressing after the prior ASCT using the registry data of the Japan Society for Hematopoietic Cell Transplantation (2001-2015) and compared overall survival (OS) between allo-SCT (n = 192) and autologous stem cell retransplantation groups (ReASCT; n = 334) based on risk factor points. Significant adverse factors for OS in all patients were (1) male sex, (2) less than partial response to SCT, (3) performance status of 2 to 4, and (4) short duration from the prior ASCT. We scored factor 2 as 1 point, factor 3 as 2 points, and factor 4 as 0, 1, or 2 points for more than 30, 9 to 30, or less than 9 months, respectively. We categorized patients into three risk subgroups based on their total points (0, 1-3, and 4-5 points), indicating the usefulness of this scoring system for prognosis prediction and treatment selection. Subgroup comparison revealed OS after ReASCT to be higher than that after allo-SCT in the intermediate-risk subgroup comprising the largest population (28.2% vs 21.5%, P < .004). We observed no significant advantages of allo-SCT over ReASCT in the low- and high-risk subgroups. These findings suggest that ReASCT is more advantageous than allo-SCT in many patients with MM relapsing/progressing after the prior ASCT. However, long-term survival patients were noted only in the allo-SCT group, and allo-SCT could exhibit clinical efficacy, particularly in the low-risk group. While further examination is warranted, allo-SCT could be a potential tool for a specific population with MM relapsing/progressing after the prior ASCT. 10.1002/hon.2688
[Multiple myeloma: Maintenance therapy after autologous hematopoietic stem cell transplantation, depending on minimal residual disease]. Solovyev M V,Mendeleeva L P,Pokrovskaya O S,Nareyko M V,Firsova M V,Galtseva I V,Davydova Yu O,Kapranov N M,Kuzmina L A,Gemdzhian E G,Savchenko V G Terapevticheskii arkhiv AIM:To determine the efficiency of maintenance therapy with bortezomib in patients with multiple myeloma (MM) who have achieved complete remission (CR) after autologous hematopoietic stem cell (auto-HSCT), depending on the presence of minimal residual disease (MRD). SUBJECTS AND METHODS:In January 2014 to February 2016, fifty-two MM patients (19 men and 33 women) aged 24 to 66 years (median 54 years), who had achieved CR after auto-HSCT, were randomized to perform maintenance therapy with bortezomib during a year. On day 100 after auto-HSCT, all the patients underwent immunophenotyping of bone marrow plasma cells by 6-color flow cytometry to detect MRD. Relapse-free survival (RFS) was chosen as a criterion for evaluating the efficiency of maintenance therapy. RESULTS:After auto-HSCT, MRD-negative patients had a statistically significantly higher 2-year RFS rate than MRD-positive patients: 52.9% (95% confidence interval (CI), 35.5 to 70.5%) versus 37.2% (95% CI, 25.4 to 49.3%) (p=0.05). The presence of MRD statistically significantly increased the risk of relapse (odds ratio 1.7; 95% CI, 1.2 to 3.4; p=0.05). Two-year cumulative risk of relapse (using the Kaplan-Meier) after auto-HSCT did not statistically significantly differ in MRD-negative patients receiving (n=15) and not receiving (n=10) maintenance therapy with bortezomib (p=0.58). After completion of maintenance treatment, 42% of the MRD-positive patients achieved a negative status. In the MRD-positive patients who had received maintenance therapy, the average time to recurrence was 5 months longer than that in the naïve patients: 17.3 versus 12.3 months. CONCLUSION:The MRD status determined in MM patients who have achieved CR after auto-HSCT is an important factor for deciding on the use of maintenance therapy. 10.17116/terarkh201789725-31
Innovative strategies minimize engraftment syndrome in multiple myeloma patients with novel induction therapy following autologous hematopoietic stem cell transplantation. Gutiérrez-García Gonzalo,Rovira Montserrat,Magnano Laura,Rosiñol Laura,Bataller Alex,Suárez-Lledó María,Cibeira María Teresa,de Larrea Carlos Fernández,Garrote Marta,Jorge Sofia,Moreno Ana,Rodríguez-Lobato Luis Gerardo,Carreras Enric,Díaz-Ricart Maribel,Palomo Marta,Martínez Carmen,Urbano-Ispizua Alvaro,Bladé Joan,Fernández-Avilés Francesc Bone marrow transplantation Autologous stem cell transplantation (PBSCT) is standard for young patients in MM and its TRM has decreased after the 2000s. Bortezomib and immunomodulatory agents (IMiDs) in MM have improved the outcome. However, they seem to boost pro-inflammatory stage increasing the incidence of engraftment syndrome (ES). Favorable factors in PBSCT such as G-CSF could increase inflammatory stage during transplant. Corticosteroids have shown an excellent response of ES and some authors propose them as prophylaxis for ES. The aim was to analyze the impact of G-CSF avoidance and corticosteroids' prophylaxis in 170 patients diagnosed of MM treated with bortezomib/IMiDs that underwent PBSCT. We established three groups: Group-I [(G-CSF_administration), 60 patients (35%)], group-II [(nonG-CSF), 60 patients (35%)] and group-III [(nonG-CSF plus corticosteroid's prophylaxis), 50 patients (30%)]. A decreased ES incidence among groups was observed: 62, 42, and 22% (P < 0.0001). The incidence of symptoms mimicking a capillary leak syndrome associated with ES dropped: 43, 32, and 0% (P = 0.03). The G-CSF avoidance and corticosteroids had impact over admission 24, 21, and 20 days (P = 0.001). The most important variables related to ES were HCT-CI >2 (p < 0.0001; HR 8.5) and risk groups (p < 0.0001; HR 7.2). Hence, G-CSF avoidance and corticosteroid's prophylaxis decrease morbidity in patients undergoing PBSCT with MM treated with bortezomib/IMiDs. 10.1038/s41409-018-0189-2
Edentulism and transplant-associated complications in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Toro Juan Jose,Gushiken Francisca Cecilia,Schneider Deanna,Lee Shuko,Haile David Johannes,Freytes Cesar Ovidio Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer PURPOSE:Patients undergoing autologous hematopoietic stem cell transplantation (HSCT) are at risk for oral complications which may cause significant morbidity. The aim of this study was to compare the incidence of toxicities and complications in edentulous and dentate patients undergoing autologous HSCT for multiple myeloma. METHODS:We conducted a retrospective case-control study to analyze the incidence of bacteremia, fever, and oral mucositis, between edentulous and dentate patients. All patients underwent dental evaluation, received dental treatment if indicated, and were cleared before transplantation. The two groups were matched for age, gender, ethnicity, disease stage, time from diagnosis to transplant, performance status, and conditioning regimen. RESULTS:A total of 45 edentulous and 90 dentate patients were enrolled. All patients were male with a median age of 60 years and a mean performance status by Karnofsky score of 90 %. Two thirds had stage III MM with a median time from diagnosis to transplantation of 12 months, and all received melphalan as part of the conditioning regimen. The incidence of bacteremia (p = 0.553), fever (p = 0.245), severity of oral mucositis (p = 0.465), and other post-transplant toxicities were similar between both groups. CONCLUSIONS:There were no significant differences in the incidence of bacteremia, fever, severity of oral mucositis, or other complications between edentulous and dentate patients with multiple myeloma after autologous HSCT. 10.1007/s00520-016-3168-4
Retrospective analysis of the efficacy and influencing factors of autologous hematopoietic stem cell transplantation for multiple myeloma. Zhang Bing-Lei,Zhou Jian,Lin Quan-De,Liu Yu-Zhang,Zhang Yan-Li,Gui Rui-Rui,Song Yong-Ping,Fang Bai-Jun Artificial organs This study aims to review the clinical efficacy and factors affecting the treatment of multiple myeloma (MM) by autologous hematopoietic stem cell transplantation (ASCT). The clinical data of 47 patients with MM from the Department of Hematology of Henan Cancer Hospital from September 2010 to July 2018 were retrospectively analyzed. At pre-transplantation of autologous cells, 25.5% were in complete remission (CR), 14.9% were in very good partial remission (VGPR) and 59.6% were in partial remission (PR). Among these cases, one case had PR after three recurrences. At post-transplantation, 51% were in CR, including two cases who received double transplantations, 27.7% were in VGPR, and 21.3% were in PR. The median follow-up time was 27.6 months (4-96 months). The 3-year progression free survival (PFS) and overall survival (OS) were 47.9% and 79.6%, respectively. The Analysis of variance (ANOVA) results revealed that factors that affected OS were international staging system (ISS) stage (P = 0.002), CR and VGPR post-transplantation (P = 0.002), while factors that affected PFS were ISS stage (P = 0.005), pre-transplant induction therapy (P = 0.032), and disease risk stratification (P = 0.017). The curative effects for PFS were CR and VGPR pre-transplantation (P = 0.013) and post-transplantation (P = 0.011). The Cox multivariate regression analysis revealed that ISS stage and CR and VGPR post-transplantation were independent prognostic factors of OS. At post-transplantation, CR and VGPR, ISS stage, and pre-transplant induction therapy were independent prognostic factors for PFS. In conclusion, ASCT can improve the clinical efficacy and survival rate of MM patients. ISS stage, CR and VGPR post-transplantation are independent prognostic factors of OS and PFS, while pre-transplant induction therapy is an independent prognostic factor for PFS. 10.1111/aor.13468
Outcome of autologous hematopoietic stem cell transplantation in refractory multiple myeloma. Veltri Lauren W,Milton Denái R,Delgado Ruby,Shah Nina,Patel Krina,Nieto Yago,Kebriaei Partow,Popat Uday R,Parmar Simrit,Oran Betul,Ciurea Stefan,Hosing Chitra,Lee Hans C,Manasanch Elisabet,Orlowski Robert Z,Shpall Elizabeth J,Champlin Richard E,Qazilbash Muzaffar H,Bashir Qaiser Cancer BACKGROUND:Despite the introduction of effective, novel agents, the outcome of patients with refractory multiple myeloma remains poor, particularly those who are refractory to both proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). Limited data are available on the role of autologous hematopoietic stem cell transplantation in this population. METHODS:Patients with refractory myeloma who underwent first autologous hematopoietic stem cell transplantation (auto-HCT) between March 2000 and October 2015 were retrospectively analyzed. Those who had primary refractory disease and those with relapsed and refractory disease were included. Disease that was refractory to at least 1 PI and at least 1 IMiD was classified as double-refractory multiple myeloma (DR-MM). RESULTS:In total, 233 patients were identified, including 105 (45%) classified with DR-MM and 128 (55%) classified with nondouble-refractory myeloma (NDR-MM). At a median follow-up of 42 months for surviving patients, at least a partial response was observed in 188 patients (81%; 83 patients in the DR-MM group [79%] and 105 patients in the NDR-MM [82%]; P = .77). A near complete response or better was observed in 52 patients (22%; 25 patients in the DR-MM group [24%] and 27 patients in the NDR-MM group [21%]; P = .77). The median progression-free survival was 17.6 months (14.4 months in the DR-MM group and 18.2 months in the NDR-MM group), and the 2-year progression-free survival rate was 38% (35% in the DR-MM group and 40% in the NDR-MM group; P = .40). The median overall survival was 48 months (38.9 months in the DR-MM group and 56.6 months in the NDR-MM group), and the 2-year overall survival rate was 74% (71% in the DR-MM group and 76% in the NDR-MM group; P = .27). CONCLUSIONS:The current findings indicate that auto-HCT is an effective and safe therapy in patients with refractory multiple myeloma, including those who are refractory to IMiDs and PIs. Cancer 2017;123:3568-75. © 2017 American Cancer Society. 10.1002/cncr.30770
Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Cavo Michele,Gay Francesca,Beksac Meral,Pantani Lucia,Petrucci Maria Teresa,Dimopoulos Meletios A,Dozza Luca,van der Holt Bronno,Zweegman Sonja,Oliva Stefania,van der Velden Vincent H J,Zamagni Elena,Palumbo Giuseppe A,Patriarca Francesca,Montefusco Vittorio,Galli Monica,Maisnar Vladimir,Gamberi Barbara,Hansson Markus,Belotti Angelo,Pour Ludek,Ypma Paula,Grasso Mariella,Croockewit Alexsandra,Ballanti Stelvio,Offidani Massimo,Vincelli Iolanda D,Zambello Renato,Liberati Anna Marina,Andersen Niels Frost,Broijl Annemiek,Troia Rossella,Pascarella Anna,Benevolo Giulia,Levin Mark-David,Bos Gerard,Ludwig Heinz,Aquino Sara,Morelli Anna Maria,Wu Ka Lung,Boersma Rinske,Hajek Roman,Durian Marc,von dem Borne Peter A,Caravita di Toritto Tommaso,Zander Thilo,Driessen Christoph,Specchia Giorgina,Waage Anders,Gimsing Peter,Mellqvist Ulf-Henrik,van Marwijk Kooy Marinus,Minnema Monique,Mandigers Caroline,Cafro Anna Maria,Palmas Angelo,Carvalho Susanna,Spencer Andrew,Boccadoro Mario,Sonneveld Pieter The Lancet. Haematology BACKGROUND:The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib-melphalan-prednisone (VMP) as intensification therapy, and bortezomib-lenalidomide-dexamethasone (VRD) consolidation therapy with no consolidation. METHODS:In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18-65 years, had symptomatic multiple myeloma stage 1-3 according to the International Staging System (ISS), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0-2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1·3 mg/m administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m administered orally on days 1-4) and prednisone (60 mg/m administered orally on days 1-4) or autologous HSCT after high-dose melphalan (200 mg/m), stratified by site and ISS disease stage. In centres with a double HSCT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1·3 mg/m either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1-21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment. FINDINGS:Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60·3 months (IQR 52·2-67·6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56·7 months [95% CI 49·3-64·5] vs 41·9 months [37·5-46·9]; hazard ratio [HR] 0·73, 0·62-0·85; p=0·0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42·1 months (IQR 32·3-49·2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58·9 months [54·0-not estimable] vs 45·5 months [39·5-58·4]; HR 0·77, 0·63-0·95; p=0·014). The most common grade ≥3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]). INTERPRETATION:This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. FUNDING:Janssen and Celgene. 10.1016/S2352-3026(20)30099-5
Pegfilgrastim improves the outcomes of mobilization and engraftment in autologous hematopoietic stem cell transplantation for the treatment of multiple myeloma. Ding Xiao,Huang Wenyang,Peng Yi,Fan Hongqiong,Zhu Yingqiao,Liu Xuelian,Yang Yanping,Guo Qiang,Qiu Lugui,Dai Yun,Zou Dehui,Jin Fengyan Annals of hematology Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 μg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34 cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34 cells than FIL (5.56 vs. 4.82 × 10/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM. 10.1007/s00277-019-03800-0