Nutrition-Related Outcomes for Autologous Stem Cell Transplantation Patients

IntroductionAutologous stem cell transplantation (ASCT) patients are at risk for malnutrition before transplantation admission as well as malnutrition acquired during their transplantation admission.Patients and MethodsIn this retrospective, observational study we examined data related to consecutive adults (n = 330) admitted for ASCT between 2014 and 2016 at the Hospital of the University of Pennsylvania. Malnutrition risk on admission (identified by the Malnutrition Screening Tool) and transplantation-associated weight loss were analyzed for independent associations with hospital length of stay, nosocomial infection, intensive care unit transfer, deconditioning, time to platelet and neutrophil engraftment, 30-day readmission, and 1-year mortality.ResultsAdults with high malnutrition risk (n = 60) had a longer median hospital stay (P = .004), longer median time to platelet engraftment (P = .022), increased nosocomial infections (P = .047), and increased 1-year mortality (P = .036). Adults with high transplantation-associated weight loss (n = 100) experienced longer hospital stays (P < .001) and more intensive care unit transfers (P = .001). Outcomes for deconditioning, time to neutrophil engraftment, and 30-day readmission did not differ significantly on the basis of nutrition risk or weight loss.ConclusionFurther research is needed to determine whether early nutrition intervention would improve these outcomes.     

自体外周血造血干细胞移植治疗多发性骨髓瘤16例临床疗效观察

目的:评价自体外周血造血干细胞移植(autologousperipheralbloodstemcelltransplantation,APBSCT)治疗多发性骨髓瘤的临床疗效。方法:16例确诊多发性骨髓瘤患者接受APBSCT,其中2例接受了二次移植,1例接受CD34+细胞筛选后的自体外周血造血干细胞移植。移植后继续常规化疗,13例患者给予α-干扰素维持治疗。结果:APBSCT可延长多发性骨髓瘤患者的无瘤生存率及总生存率,该组患者3年、5年无瘤生存率分别为18.75%±9.75%、0,平均无瘤生存时间为24.8个月。3年、5年总生存率分别为41.25%±12.72%、18.33%±10.77%,平均总生存时间为37.4个月。本组移植患者的CR率高,达76.92%,接近国外报道。而且,移植后造血重建快,移植相关并发症少。结论:APBSCT是治疗多发性骨髓瘤、改善其预后的重要手段。     

Superior Survival in African American Patients Who Underwent Autologous Stem Cell Transplantation for Multiple Myeloma

Introduction/BackgroundAfrican American (AA) individuals have a twofold higher incidence of multiple myeloma (MM) compared with other racial groups. Outcomes are affected by factors such as disparate access to care as well as differences in disease biology.Patients and MethodsWe conducted a single-institution analysis to evaluate the effect of AA race on outcomes of MM patients who underwent autologous stem cell transplantation (ASCT) in the pre-novel and novel agent era.ResultsSixty-one (47%) patients were AA and 69 (53%) were non-AA. Overall, 78 (60%) patients received any novel agent before transplantation and 52 (40%) received only chemotherapy. More non-AA patients received initial induction with a proteasome inhibitor (40 [60%] vs. 17 [28%]; P = .0007), and were treated with post-ASCT maintenance therapy (28 [41%] vs. 14 [23%]; P = .04). Time from diagnosis to ASCT in AA patients was 10 (range, 4-144) versus 8 (range, 3-54) months in non-AA patients (P = .01). Despite this, treatment-free survival (TFS) was equivalent between the 2 groups (x vs. y). Furthermore, AA patients had greater median overall survival (OS) compared with non-AA patients (not reached vs. 108 months; P = .03) and significantly improved OS in multivariable Cox proportional hazards models (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.81; P = .017). Median OS, landmarked at the time of relapse, was improved in AA patients (not reached vs. 68 months for P = .05).ConclusionOur study showed with long follow-up, equivalent TFS after ASCT in AA and non-AA patients yet improved OS. Post relapse survival is improved in AA patients suggesting a better response to salvage therapy.     

Autologous Stem Cell Transplantation for Multiple Myeloma: Identification of Prognostic Factors

IntroductionThe purpose of this study was to evaluate the effect of prognostic factors on the outcome of patients with MM after ASCT.Patients and MethodsWe analyzed results of 170 consecutive patients (121 male and 49 female) of MM who underwent ASCT. Patients' median age was 52 years (range, 26-68 years). High dose melphalan (200 mg/m²) was used for conditioning. One hundred thirty-two patients (77.6%) had evidence of chemosensitive disease before transplant. Response was assessed using European Group for Blood and Bone Marrow Transplantation criteria.ResultsPost ASCT 44.7% of patients achieved CR, 24.7% had very good partial response (VGPR), and 21.2% had partial response (PR). Presence of pretransplant chemosensitive disease (CR, VGPR, and PR) and transplant within 12 months of diagnosis for years before 2006 were associated with higher response rates on multivariate analysis. At a median follow-up of 84 months, median overall (OS) and event-free survival (EFS) is 85.5 and 41 months, respectively. Estimated OS and EFS at 60 months is 62 ± 0.04% and 41 ± 0.04%, respectively. Patients who responded to transplant (CR, VGPR, and PR) had a longer OS (P < .001) and EFS (P < .001). Additionally, patients who achieved CR post transplant had a longer OS (P < .001) and EFS (P < .001). Patients who received novel agents for induction pretransplant had a longer OS (P < .001) and EFS (P < .002).ConclusionOutcome after ASCT is better for myeloma patients with pretransplant chemosensitive disease and those who achieve CR after transplant.     

18F-FDG PET/CT在多发性骨髓瘤诊断中的应用

摘 要：［目的］ 探讨18F-FDG PET/CT对于多发性骨髓瘤的诊断价值。［方法］ 选择拟诊断为骨髓瘤的30例患者,利用CT、PET及PET/CT 3种诊断方法分别进行诊断,并与病理结果（23例骨髓瘤,7例骨骼转移瘤）进行对照,分析不同方法的诊断灵敏度和特异性。［结果］ PET诊断的灵敏度为34.8%~47.8%,特异性为57.1%~71.4%,诊断符合率为40.0%~50.0%;CT诊断上述指标分别为73.9%~86.9%、71.4%~85.7%和80.0%~86.6%;PET/CT诊断分别为82.6%~100%、42.9%~71.4%和 80.0%~90.0%。PET/CT诊断的灵敏度和诊断符合率均高于PET和CT。本研究中观察到：（1）骨髓瘤与骨骼转移瘤均容易侵犯脊柱、骨盆,四肢及肋骨。骨髓瘤侵犯颅骨的几率高于骨骼转移瘤。（2）骨髓瘤病灶的SUVmax为3.46±1.52,骨转移瘤病灶为4.59±3.39,差异无统计学意义（t=1.270,P=0.216）。骨髓瘤病灶SUVmax与健康者不同部位骨骼（颅骨、脊柱、骨盆、四肢、肋骨）的SUVmax差异均有统计学意义（P均＜0.05）。（3）颅骨“穿凿”样骨质破坏,肋骨膨胀性骨质破坏、脊柱骨质疏松样改变、18F-FDG的不均匀分布、轻微性分布等特征可以提高骨髓瘤的诊断率。（4）CT影像特征是PET/CT诊断骨髓瘤的的关键因素。［结论］ 18F-FDG PET/CT在诊断骨髓瘤具有较高的价值,但需与其它多发骨骼转移瘤相鉴别。     

Hematopoietic Progenitor Cell Mobilization for Autologous Stem Cell Transplantation in Multiple Myeloma in Contemporary Era

Successful stem cell mobilization and adequate harvesting of hematopoietic progenitor cells (HPCs) is necessary for patients with multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (ASCT). Several advances have increased the efficiency and yield of HPC collection methods, and sufficient CD34⁺ cell collection can be expected for most patients with MM considered to be ASCT candidates. However, in some patients, HPCs will fail to mobilize and an adequate number of CD34⁺ cells will not be collected. In our review, we have discussed the various strategies available for mobilizing HPCs in patients with MM and the evolution of these strategies over time. We have also discussed the concept of mobilization failure, the factors predictive of poor mobilization, and the potential mobilization regimens for such patients.     

Progression to Symptomatic Multiple Myeloma Predicted by Texture Analysis-Derived Parameters in Patients Without Focal Disease at 18F-FDG PET/CT

This retrospective study is focused on the possible clinical implications of texture analysis-derived PET parameters in patients with smoldering multiple myeloma. Several texture features are significantly associated with progression to symptomatic multiple myeloma and with a shorter time to progression. The results of this study may lead to early identification of patients who could benefit from specific therapies.Background: The aim of the study was to determine whether positron emission tomography parameters derived from texture analysis of axial and peripheral skeleton predict progression to symptomatic multiple myeloma (MM) in patients undergoing 18F-​fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) without evidence of focal sites of ¹⁸F-FDG uptake. Patients and Methods: Patients with smoldering MM who underwent ¹⁸F-FDG PET/CT from May 2014 to June 2018 were retrospectively reviewed. Volumes of interest (VOIs) were placed on T5-T7 and L2-L4, iliac crests, and femoral diaphyses. Dedicated software (LIFEx) allowed us to obtain PET-derived first-, second-, and higher order texture features. Possible associations between PET parameters and progression to symptomatic MM were determined. Kaplan–Meier curves allowed to assess time to progression (TTP) based on the PET parameters. Results: Forty-five patients were included: 26 patients (58%) did not meet the criteria for symptomatic MM, but 19 patients (42%) progressed to symptomatic MM. Several texture features extracted from VOIs placed on iliac crests and femoral diaphyses were significantly associated with progression to symptomatic MM and with a shorter TTP (P < .05); conversely, the above-mentioned parameters extracted from VOIs placed on T5-T7 and L2-L4 did not significantly differ among the patients with regard to their progression to symptomatic MM and length of TTP, except for the gray-level zone length matrix–short-zone low-gray-level emphasis and gray-level zone length matrix–low gray-level zone emphasis. Particularly, second- and higher order texture features showed a significant association with the above-mentioned outcomes. Conclusion: Texture features derived from PET may be an expression of subtle disease distribution in the axial and peripheral bone marrow.     

异基因造血干细胞移植在年轻多发性骨髓瘤患者治疗中的应用

目的探讨异基因造血干细胞移植在年轻多发性骨髓瘤治疗中的疗效及安全性。方法回顾性分析我科2003年4月至2012年6月行清髓异基因造血干细胞移植(allo-SCT）的22例多发性骨髓瘤患者,中位年龄为44.5岁（30～54岁）。所有患者随访至2012年10月。中位随访时间11月（0.9～92月）。结果22例患者移植前完全缓解率为13.6%,移植后完全缓解率达63.6%。100天内移植相关死亡率（TRM）为9.1%。1年内TRM为22.7%。1年内的复发率为13.6%。随访期内总生存率为68.2%,无进展生存率为50%。多因素分析未显示年龄、性别、移植前缓解状态及诊断至移植时长是影响总生存期的独立危险因素。结论清髓的异基因造血干细胞移植用于年轻多发性骨髓瘤患者具有较好的疗效及安全性,且一年内复发率较低。     

Immune Signatures Associated With Clonal Isotype Switch After Autologous Stem Cell Transplantation for Multiple Myeloma

BackgroundHigh-dose chemotherapy and autologous stem cell transplantation (ASCT) are integral components of the overall treatment for patients with multiple myeloma (MM) aged ≤ 65 years. The emergence of oligoclonal immunoglobulin bands (ie, immunoglobulins differing from those originally identified at diagnosis [termed clonal isotype switch (CIS)]) has been reported in patients with MM after high-dose chemotherapy followed by autologous stem cell transplantation. However, the clinical relevance and the correlation with immune reconstitution remains unclear.Patients and MethodsPatients with MM who had undergone ASCT from 2007 to 2016 were included in the present study. The percentage of natural killer cells, B-cells, and T-cells was measured using flow cytometry in pre- and post-ASCT bone marrow samples. CIS was defined as the appearance of a new serum monoclonal spike on serum protein electrophoresis and immunofixation that differed from original heavy or light chain detected at diagnosis.ResultsA retrospective analysis of 177 patients with MM who had undergone ASCT detected CIS in 39 (22%). CIS after ASCT correlated with improved progression-free survival (52.2 vs. 36.6 months; P = .21) and overall survival (75.1 vs. 65.4 months; P = .021). Patients with a relapse had an isotype that differed from a CIS, confirming the benign nature of this phenomenon. CIS was also associated with lower CD8 T-cell percentages and a greater CD4/CD8 ratio (2.8 vs. 0.2; P = .001) compared with patients who did not demonstrate a CIS, suggestive of more profound T-cell immune reconstitution in this group.ConclusionTaken together, our data have demonstrated that a CIS is a benign phenomenon and correlates with a reduced disease burden and enriched immune repertoire beyond the B-cell compartment.     

Timing of Autologous Stem Cell Transplantation for Multiple Myeloma in the Era of Current Therapies

BackgroundAutologous stem cell transplantation (SCT) during the initial treatment of multiple myeloma has been shown to improve progression-free survival (PFS) but not overall survival (OS). While awaiting further prospective data, we retrospectively analyzed the outcomes of patients at our program.Patients and MethodsWe included consecutive patients with newly diagnosed myeloma who had undergone stem cell harvest (SCH) from 2005 to 2014 and separated them into early (SCT within 12 months of diagnosis) and delayed (all others, including SCT not yet) groups. The outcomes were OS, PFS to first relapse, and PFS to second relapse.ResultsOf the 514 patients who had undergone SCH, 227 were in the early and 287 in the delayed groups. Patients in the delayed group who had undergone SCT had received more therapy before SCT (55% had received ≥ 2 lines vs. 6% in the early group; P < .001), had had more progressive disease at SCT (34% vs. 4%; P < .001), had received melphalan doses < 200 mg/m² (22% vs. 10%; P = .001), and had had lower rates of very good partial response or better after SCT (58% vs. 79%; P = .001). On multivariable analysis, no differences were found in median OS (90 vs. 84 months; P = .093), PFS to first relapse (40 vs. 37 months; P = .552), or PFS to second relapse (54 vs. 52 months; P = .488) between the early and delayed groups.ConclusionDelaying SCT did not affect OS or even PFS to second relapse in our cohort of patients with newly diagnosed myeloma who had received current era induction therapy.     

Prognostic Factors in Autologous Stem Cell Transplantation for Multiple Myeloma: An EBMT Registry Study

Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months.

The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression-free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease.

We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation.     

氨磷汀在自体外周血干细胞移植治疗多发性骨髓瘤中的口腔黏膜保护作用

[目的]探讨氨磷汀在自体外周血干细胞移植（APSCT）治疗多发性骨髓瘤（MM）中的口腔黏膜保护作用.[方法]10例MM患者进行了大剂量马法兰（200mg/m^2）和APSCT,其中4例在大剂量马法兰预处理前加用氨磷汀（740mg/m^2）,6例未用.[结果]加用氨磷汀的4例中出现3级口腔炎1例,未用氨磷汀的6例出现3级口腔炎3例,其中1例使用了吗啡控制疼痛.加用氨磷汀的4例患者中,CR 2例,PR 2例;未加用氨磷汀的6例患者中,CR3例,PR2例.[结论]初步提示氨磷汀对降低大剂量马法兰对口腔黏膜的毒性是可行有效的,同时不影响化疗的抗肿瘤作用.     

Treatment Intensification With Autologous Stem Cell Transplantation and Lenalidomide Maintenance Improves Survival Outcomes of Patients With Newly Diagnosed Multiple Myeloma in Complete Response

Background

High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy.

Autologous Transplantation with Tumor-Free Graft: A Model for Multiple Myeloma Patients

The importance of obtaining a tumor-free graft for autologous transplantation in cancer patients has been debated extensively in the last decade and is still unresolved largely because it is believed that relapse is more likely to originate from the host and not from the graft. This is in spite of recent indications that the main source of relapse is the graft. In this review article we bring forward evidence that the currently used grafts, whether from peripheral blood or bone marrow, harbour significant number of tumor cells before and even after purging with currently available purging protocols. We believe that the use of a tumor-free graft is the only way to obtain a valid assessment of the efficacy of high dose radio-chemotherapy, and is the only methodology to increase the probability to achieve long term survival following AT. Accordingly, we describe in detail a procedure to obtain a tumor-free graft, designed for the treatment of multiple myeloma patients based on flow-sorting of CD34+ stem cells.     

Initial Therapy of Multiple Myeloma in Patients who are Candidates for Stem Cell Transplantation

Opinion statement Multiple myeloma (MM), a B cell hematologic malignancy involving plasma cells, responds to a variety of drugs including alkylators, steroids, anthracyclines, immunomodulators and proteosome inhibitors. The disease, however, remains largely incurable for the majority of patients. For patients who are suitable candidates, high dose chemotherapy with autologous stem cell support (ASCT) after induction therapy has been shown to improve response rates, progression free survival and overall survival compared to conventional chemotherapy. The availability of new drugs including thalidomide, lenalidomide and bortezomib has rapidly changed induction strategies. These drugs have been combined with corticosteroids, alkylators and anthracyclines to treat front-line patients with MM. Preliminary, phase 1–2 studies have indicated very high response rates and complete response rates formerly only seen with ASCT. Emerging data from randomized trials suggest that older regimens such as vincristine, adriamycin and dexamethasone (VAD) are not as effective for induction as newer combinations. Thus new regimens incorporating novel agents should improve overall response rates, increase complete responders which should translate into improved progression free and overall survival.     

硼替佐米联合自体造血干细胞移植治疗多发性骨髓瘤的临床分析

目的探讨硼替佐米联合自体造血干细胞移植治疗多发性骨髓瘤的疗效和安全性。方法对1例轻链型多发性骨髓瘤患者,采用VTD方案（硼替佐米1.3 mg/m2,d 1、4、8、11;沙利度胺200 mg,d 1～14;地塞米松10 mg,d 1～4、d 9～12）化疗3个周期获得完全缓解后再行自体造血干细胞移植,监测M蛋白、肝肾功能、骨髓像、血象等指标,移植后再行白介素-2的免疫治疗。结果自体造血干细胞移植后患者造血重建顺利,相关并发症控制较好,随访至今一直无病生存。结论硼替佐米联合自体造血干细胞移植治疗多发性骨髓瘤是安全有效的。     

Outcomes of Daratumumab,Pomalidomide, and Dexamethasone,Followed by High-dose Chemotherapy and Autologous Stem Cell Transplantation,in Patients With Relapsed/Refractory Multiple Myeloma

BackgroundThe number of therapeutic options for patients with relapsed/refractory multiple myeloma (RRMM) has increased significantly. Our institute treated a series of patients with RRMM using DPd (daratumumab, pomalidomide, dexamethasone) as salvage therapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT).Patients and MethodsWe treated 18 patients with RRMM from May 2016 to April 2020, with DPd as salvage therapy, followed by HDCT and ASCT. DPd was administered as daratumumab 16 mg/kg weekly for cycles 1 and 2, every 2 weeks for cycles 3 to 6, and then every 4 weeks. Pomalidomide was given at 4 mg orally on days 1 to 21 of a 28-day cycle, and dexamethasone at 20 or 40 mg weekly.ResultsThe patients had received a median of 2 (range, 1-4) previous regimens. Of the 18 patients, 13 (72%) had received ASCT before this treatment. In addition, 78% had disease refractory to proteasome inhibitors, 78% refractory to immunomodulatory agents, and 72% double refractory to immunomodulatory agents and proteasome inhibitors. The overall response rate after salvage treatment with DPd was 100% and at day 100 after ASCT was 100%; 67% had achieved a complete response or better and 78% had achieved a very good partial response or better. No treatment-related mortality had occurred by day 100. The 2-year progression-free and overall survival rates were 83.3% and 94.4%, respectively. The most common grade ≥ 3 adverse events were thrombocytopenia (100%), neutropenia (100%), and neutropenic fever (67%).ConclusionsDPd as salvage therapy, followed by HDCT and ASCT, demonstrated deep, durable, and clinically meaningful responses with a manageable safety profile in patients with RRMM.     

Trajectory of Symptoms in Patients Undergoing Autologous Stem Cell Transplant for Multiple Myeloma: A Population-Based Cohort Study of Patient-Reported Outcomes

BackgroundAutologous stem cell transplant (ASCT) is an established treatment for patients with newly diagnosed multiple myeloma (NDMM). Understanding the symptom burden associated with ASCT may be an important consideration for patients with NDMM when selecting treatment options.Patients and MethodsWe conducted a population-based study of patients who underwent an ASCT for NDMM in Ontario, Canada, between 2007 and 2018. The patient-reported outcome, Edmonton Symptom Assessment System (ESAS) score, which captures nine common cancer-associated symptoms and is routinely collected at all outpatient visits, was linked to provincial administrative healthcare data. The monthly prevalence of moderate or severe symptoms (ESAS ≥ 4) each month in the first year following ASCT was analyzed. A multivariable logistic regression model was used to identify factors associated with moderate to severe symptoms.ResultsIn our final cohort of 1969 patients who had undergone an ASCT, a total of 12,820 unique assessments were captured. Symptom burden was highest at 1 month post-ASCT, with moderate to severe tiredness and impaired well-being being the two most common symptoms. Symptom burden substantially improved by 3 months post-ASCT, reaching a new baseline for the year following. On multivariable analysis, female sex, increased co-morbidities, earlier year of diagnosis, and myeloma-related end-organ damage (specifically, bone and kidney disease) were associated with a higher odds of reporting moderate to severe symptoms.ConclusionIn this large population-based study using patient-reported outcomes, there was a substantial burden of symptoms noted among NDMM patients 1 month post-ASCT, which improved over time. Tailored supportive care interventions should focus on strategies to optimize management of identified symptoms.