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Allogeneic stem cell transplant (allo SCT) for multiple myeloma (MM) is potentially curative in some, while toxic in many others. We retrospectively analyzed 85 patients diagnosed with MM who underwent allo SCT as frontline or salvage therapy between 2000 and 2022 at Mayo Clinic Rochester and examined patient outcomes and prognostic markers. Overall survival (OS), progression free survival (PFS), treatment related mortality (TRM), and relapse rates (RR) were estimated using the Kaplan Meier method and competing risk models. Median follow-up was 11.5 years. Median OS and PFS were 1.7 and 0.71 years, respectively. Five-year OS and PFS were 22.2% and 15.1%, respectively. One-year TRM was 23.5%. Twelve patients demonstrated durable overall survival, living 10+ years beyond their allo SCT. This subgroup was more likely to have no or one prior auto SCT (p = 0.03) and to have been transplanted between 2000 and 2010 (p = 0.03). Outcomes were poor in this cohort with long follow-up, with few patients surviving 5 years or more, and most relapsing or dying within 2 years. We would expect better outcomes and tolerability with an expanded array of novel therapeutics and would prefer them to allo SCT., (© 2023. Springer Nature Limited.)

Multiple Myeloma patients eligible for autologous hematopoietic transplantation (AHT) typically receive 3-6 cycles of induction therapy before transplant. The last induction cycle is completed 2-4 weeks prior to mobilization. We evaluated the impact of the time interval between end of induction and AHT on progression-free survival (PFS) and overall survival (OS). A total of 1055 patients who underwent AHT were identified. The median time to transplant (TTT) was 33 days (27-42 quartile range). Patients with less than 33 days of TTT had significantly prolonged PFS (35.6 vs. 32.1 months, p < 0.03) but non-significant OS differences compared to those with more than 33 days. Quartile comparisons showed that patients in the 1st quartile (less than 27 days) had significantly prolonged PFS (36.7 vs. 30.9 months, p < 0.01) compared to the 4th quartile group (more than 42 days). In a subgroup analysis of patients with partial or worse biochemical response prior to transplant, patients in the 1st quartile had significantly prolonged PFS (37.7 vs. 28.7 months, p < 0.04) compared to the 4th quartile group. In conclusion, we showed that a prolonged TTT is associated with inferior outcomes compared to tighter chemotherapy schedules. This finding was especially prevalent in patients with partial response at induction., (© 2022. The Author(s).)

We retrospectively reviewed 292 patients who received a second line of therapy post ASCT for their light chain amyloidosis. Most patients (40%) were treated with an alkylator + PI ± dex or PI ± dex followed by an alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex (26%), an alkylator ± steroid or steroid monotherapy (19%), a 2nd-gen IMiD + PI ± dex (6%), an alkylator + thalidomide ± dex (5%), or daratumumab-based therapy (4%). The rate of CR or VGPR was 70% among the daratumumab-based group, 62% in the alkylator + PI ± dex or PI ± dex group, 55% in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 47% in the 2nd-gen IMiD + PI ± dex group, 24% in the alkylator ± steroid or steroid monotherapy group, and 18% in the alkylator + thalidomide ± dex group. The median OS was NR for the 2nd-gen IMiD + PI ± dex group and the daratumumab group, 130.4 months in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 100 months for the alkylator + PI ± dex or PI ± dex group, 36 months for the alkylator ± steroid or steroid monotherapy group, and 21 months for the alkylator + thalidomide ± dex group (P < 0.0001). The median OS was 100 months in patients who received melphalan 200 mg/m 2 compared to 41 months in the 140 mg/m 2 group (P < 0.0001). In conclusion, patients receiving novel therapy post ASCT and melphalan conditioning dosing at 200 mg/m 2 at diagnosis had better outcomes., (© 2022. The Author(s).)

We conducted a retrospective study comparing posttransplant outcomes between myeloma patients receiving conditioning melphalan on day-2 vs day-1 for autologous stem cell transplant. Between January 2017 and December 2018, 201 patients received melphalan on day-2 and 166 on day-1 prior to stem cell infusion. Baseline disease and clinical characteristics between the two groups were similar. Although rates of hospitalization were similar between the cohorts, duration of hospital admission was longer for day-1 (median 7 days for day-1 vs 5 days for day-2, p = 0.003). Rates of fever were higher in the day-1 cohort (69% vs 49%, p = 0.0002). Time to platelet and neutrophil engraftment was significantly longer in the day-1 cohort (platelet engraftment median days 17 for day-1 vs 15 for day-2, p < 0.0001, neutrophil engraftment median days 16 for day-1 vs 16 for day-2, p = 0.025). Overall response rate was similar between the cohorts (99% for day-1, vs 100% for day-2). Day-2 melphalan infusions should be considered in preference for day-1 protocols, given the clinically significant delay in platelet and neutrophil engraftment and longer duration of hospitalization with day-1 infusions.

The prognostic impact of increased beta-2 microglobulin (B2M) in patients with light chain (AL) amyloidosis undergoing autologous stem cell transplantation (ASCT) is unknown. The Mayo 2012 stage and increased bone marrow plasma cell (BMPC) percentage are known predictors for survival. Increased B2M is predictive of survival in patients with multiple myeloma. We evaluated the prognostic role of B2M in patients with newly diagnosed AL undergoing ASCT. We retrospectively reviewed patients with a diagnosis of AL amyloidosis who were treated with ASCT between July 1996 and September 2017. Patients with a creatinine level >1.2 mg/dL were excluded, because that affects B2M levels. The receiver operator characteristic curve was used to determine the best cutoff for B2M before ASCT in predicting survival, which was 2.5 µg/mL, which was also the upper limit of normal in our laboratory. Baseline characteristics were compared between patients with B2M >2.5 µg/mL and ≤2.5 µg/mL. Progression-free survival (PFS) was defined as the time from ASCT to relapse or death, whichever occurred first. Overall survival (OS) was calculated from the time of ASCT to death of any cause. Univariate and multivariate analyses were done for OS. Five hundred and ten patients were identified, 222 of whom (44%) had a B2M >2.5 µg/mL. These patients were more likely to be older (median age, 61 versus 57 years; P = .0002), to have Mayo 2012 stage III/IV disease (33% versus 8%; P < .0001), to have more than 2 organs involved (25% versus 14%; P = .001), and to have ≥10% BMPCs (56% versus 40%; P = .0002) compared with patients with B2M ≤2.5 µg/mL. The median PFS and OS were shorter in patients with B2M >2.5 µg/mL (median PFS, 64 months versus 80 months [P = .03]; median OS, 104.9 months versus 175.5 months [P < .0001]). On univariate analysis, predictors for OS included age >60 years (hazard ratio [HR], 1.61; P = .001), Mayo 2012 stage III/IV (HR, 3.36; P < .0001), more than 2 organs involved (HR, 1.36; P = .07), ≥10% BMPCs (HR, 1.5; P = .005), melphalan conditioning with 200 mg/m 2 (HR, .29; P < .0001), B2M >2.5 µg/mL (HR, 1.82; P < .0001), and transplantation during or after 2010 (HR, .4; P = .0006). On multivariate analysis, only Mayo 2012 stage III/IV (HR, 1.89; P = .005), melphalan conditioning with 200 mg/m 2 (HR, .39; P < .0001), B2M >2.5 µg/mL (HR, 1.84; P = .003), and transplantation performed during or after 2010 (HR, .58; P = .03) remained independent predictors of OS. Our findings identify B2M >2.5 µg/dL before ASCT as an independent predictor for OS in patients with AL amyloidosis and normal kidney function and should be routinely measured., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Autologous stem cell transplantation (ASCT) is an integral component of the therapeutic arsenal in multiple myeloma. Given that overall survival (OS) is comparable between patients receiving up-front or delayed ASCT, some opt to collect stem cells and postpone transplant until the time of disease progression (i.e., salvage ASCT). It is unknown if induction should be repeated prior to salvage ASCT, or if patients should proceed directly. We identified 234 patients who underwent salvage ASCT at our institution: 188 (80%) were re-induced, whereas 46 (20%) proceeded directly without re-induction. There was no significant difference in time to next therapy (TNT) or OS from Day 0 between the two groups. Patients who were re-induced had a nonsignificant trend towards a higher rate of complete response post-ASCT (45 vs. 33%, p = .12). In multivariate models, re-induction did not affect TNT/OS. In the subgroup of 188 patients who were re-induced, patients with relapsed/refractory disease at the time of ASCT had significantly shorter TNT/OS compared to patients with deeper pre-ASCT responses. In summary, there was no survival difference for patients who were re-induced before salvage ASCT. However, many factors affect the decision to re-induce, and prospective studies would be required to discern its role definitively.

Autologous stem cell transplant (ASCT) for multiple myeloma (MM) is associated with diarrhea during the peri-transplant period. We aimed to appraise mechanisms of peri-ASCT diarrhea in a prospective, longitudinal study of patients with MM. We compared by repeated measures (RM)-ANOVA daily bowel movements (BMs) and consistency [7-point Bristol Stool Form Scale (BSFS)], fecal calprotectin (intestinal inflammation), 13 C-mannitol excretion in urine 0-2 h (small intestinal permeability), fasting serum C4 (bile acid synthesis) and total and primary bile acid in stool samples during baseline, peri-transplant period (Days 5-7 after stem cell infusion), and after hematological recovery post-ASCT. The 12 (5F, 7M) patients' median age was 61 y (IQR 54.8-63.3). All participants reported increased BMs (increase of 2 and 1 per day with and without engraftment syndrome, respectively). There were no significant increases in serum C4, total fecal bile acids, or intestinal permeability. Relative to patients without engraftment syndrome, four participants with engraftment syndrome had looser stool consistency (mean 2.6 points higher BSFS compared to without engraftment syndrome), increased primary fecal bile acids relative to baseline (>33 µmol/L vs. 6 µmol/L without engraftment syndrome), and increased fecal calprotectin compared to baseline (313 μg/mL vs. 35.6 μg/mL without engraftment syndrome; p = 0.06). Engraftment syndrome post-ASCT is associated with increased fecal primary bile acids.

Autologous stem cell transplantation (ASCT) remains a mainstay in the treatment of multiple myeloma (MM). While the procedure is generally safe, toxicities associated with high-dose melphalan conditioning are common and significantly affect patient quality of life. Recently, a propylene glycol-free melphalan formulation (PG-free MEL; Evomela®) was approved by the United States Food and Drug Administration as an ASCT-conditioning regimen for MM. PG-free MEL is more soluble and stable than propylene glycol-solubilized melphalan (PG-solubilized MEL; Alkeran®). As such, there is speculation that it could decrease toxicities and increase the efficacy of ASCT. We compared the outcomes of patients conditioned with PG-free MEL (n = 216) to PG-solubilized MEL (n = 200) at our institution. The baseline characteristics were similar between the two groups. After Day +0, there were no differences in terms of hospitalizations, neutropenic fevers, intravenous granisetron requirement, World Health Organization grade ≥ 2 oral/esophageal mucositis, intravenous fluid requirement, or narcotic requirement. However, PG-free MEL patients had a higher incidence of diarrhea, which was mostly C. difficile-negative (82% vs. 71%, P = 0.015*). Day + 100 hematologic responses and progression-free survival after ASCT were comparable. In summary, we demonstrate that switching to PG-free MEL did not significantly reduce short-term complications of ASCT or improve outcomes in MM.

Over the last two decades, the utilization of various novel therapies in the upfront or salvage settings has continued to improve survival outcomes for patients with Multiple Myeloma (MM). Thus, the conventional role for hematopoietic stem cell transplantation (HSCT) in MM either in the form of an autologous stem cell transplant (ASCT) or an allogeneic stem cell transplant (Allo-SCT) warrants re-evaluation, given the aforementioned clinical advances. Here, we present a consensus statement of our multidisciplinary group of over 30 Mayo Clinic physicians with a special interest in the care of patients with MM and provide evidence-based recommendations on the use of HSCT in MM. We specifically address topics that include the role and timing of an ASCT for MM in the era of novel agents, eligibility for an ASCT, post-ASCT consolidation, and maintenance options, and finally the utility of an upfront tandem ASCT, salvage second ASCT, and an allo-SCT in MM.

Myeloma patients failing to achieve a complete response post autologous stem cell transplantation are heterogeneous, some ultimately achieving deeper responses and prolonged remission, whilst others relapse rapidly with poor outcomes. We evaluated the prognostic impact of the plasma cell proliferative index (PCPI) post-therapy, in 382 patients with myeloma failing to achieve complete response at 100 days post-transplant. Sixty percent (n = 230) of patients had zero clonal or too few clonal plasma cells to accurately assess PCPI (No PCPI). The remaining 40% (n = 152) of patients had PCPI performed with 79% (n = 120) having a low PCPI and 21% (n = 32) having an elevated PCPI. Patients with an elevated PCPI had significantly shorter progression free and overall survival. The median PFS was 8 months for elevated PCPI vs. 19 months for low PCPI vs. 24 months for no PCPI (p < 0.0001). The median OS was 27 months for elevated PCPI vs. 79 months for low PCPI vs. not reached for no PCPI, p < 0.0001). On multivariable analysis post-therapy PCPI was an independent predictor of progression free and overall survival. The PCPI post-therapy is a powerful predictor of survival and risk stratifies myeloma patients failing to achieve complete response early in the disease course.

We retrospectively reviewed all patients (n = 243) receiving bortezomib, lenalidomide, and dexamethasone (VRd) induction followed by autologous stem cell transplantation (ASCT) for multiple myeloma at the Mayo Clinic between January 2010 and April of 2017. Median age was 61 (interquartile range, 55-67) with 62% of patients being male. High-risk cytogenetic abnormalities (HRA) were present in 34% of patients. A total of 166 (68%) patients received some form of maintenance/other therapy post transplant (no maintenance (NM, n = 77), lenalidomide maintenance (LM, n = 108), bortezomib maintenance (BM, n = 39), and other therapy (OT, n = 19)). Overall response rate at day 100 post ASCT was 99% (CR 42%) with CR rate increasing to 62% at time of best response post transplant. Two year and 5 year overall survival rates were 90% and 67%, respectively, with an estimated median overall survival (OS) and progression-free survival (PFS) of 96 and 28 months, respectively. HRA was associated with a worse OS but not PFS (median OS: not reached for standard risk vs 60 months for HRA, P = 0.0006; median PFS: 27 months for standard risk vs 22 months for HRA, P = 0.70). The combination of VRd followed by ASCT is a highly effective regimen producing deep and durable responses in many patients.

The optimal duration of induction therapy (IT) in transplant-eligible multiple myeloma (MM) patients in not well defined, resulting in a wide variation in clinical practice. The objective of our study was to determine whether the duration of IT in patients undergoing upfront autologous stem cell transplantation (ASCT) has an impact on progression-free survival (PFS) in the era of proteasome inhibitors and immunomodulatory drugs. A total of 596 patients who underwent ASCT at Mayo Clinic between 2007 and 2014 were included. The patients were divided into two cohorts based on the duration of IT: IT ≤ 4 and IT > 4 months. At a median follow-up of 54·5 months from ASCT, the median PFS in the IT ≤ 4 group was 28 months [95% confidence interval (CI), 25-33], compared to 26 months in the IT > 4 group (95% CI, 24-31) [P = 0·605]. There was no significant difference in overall survival (OS) in the two groups (P = 0·904). The lack of impact of IT duration on PFS and OS was consistent in subgroups with high-risk features at diagnosis (International Staging System III or high-risk cytogenetics) and different depths of pre-transplant response [≥very good partial response (VGPR) and

Systems have been put in place in the Mayo Clinic Stem Cell Transplantation program to reduce day-100 all-cause mortality. Currently our mortality has been reduced to 0.3%. Patients can undergo transplant as an outpatient, with a median hospital duration of 0 days and only 25% of patients requiring a hospital stay of 5 days or greater. Outpatient transplantation is safe and reduces patient-incurred costs., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Circulating plasma cells at diagnosis, prior to auto-transplant and at relapse have a negative impact on survival in multiple myeloma. However, the impact of kinetics of circulating plasma cells along the course of illness has not been defined. We have analyzed 247 newly diagnosed multiple myeloma patients undergoing early auto-transplant who had paired evaluation of circulating plasma cells at diagnosis and pre-transplant by 6-color flow cytometry. A total of 117 patients had no detectable circulating plasma cells at both time points (CPC-/-), 82 had circulating plasma cells at diagnosis followed by complete eradication after induction (CPC+/-) and 48 had circulating plasma cells at transplant, including persistence of cells (CPC+/+; n=45) or emergence of new cells (CPC-/+; n=3) after induction. The rate of post-transplant stringent complete response was 32% in the CPC-/-, 30% in CPC+/- and 12% in CPC+/+ or -/+ groups ( P =0.018). At a median follow up of 58 months from transplantation, the median progression-free survival in the 3 respective groups were 30, 24 and 14 months, and the 5-year overall survival rates were 83%, 70% and 43% ( P <0.001 for both comparisons). On a multivariate analysis for overall survival, the risk of mortality was higher in CPC +/- (hazard ratio 2.7, 95%CI: 1.3-5.8; P =0.009) and CPC+/+ or -/+ (hazard ratio 5.7, 95%CI: 2.5-13.1; P <0.001) groups compared to the CPC-/- group. Monitoring for circulating plasma cells before induction therapy and before transplant by 6-color flow cytometry is predictive of survival in newly diagnosed myeloma and should be incorporated into clinical trials., (Copyright© 2017 Ferrata Storti Foundation.)

The impact of depth of response and minimal residual disease (MRD) status on survival is not well defined in multiple myeloma (MM) with high-risk (HR) cytogenetics because of the low representation of such patients in clinical trials. We have evaluated the impact of post-transplant stringent complete response (sCR) and MRD status on progression-free survival (PFS) and overall survival (OS) in 185 consecutive MM patients with HR fluorescence in situ hybridization cytogenetics undergoing upfront autologous stem cell transplantation between 2007 and 2015 in our institution. The median age at transplant was 61 years. Post-transplant sCR was achieved by 42 patients (23%). Patients achieving sCR had a superior PFS (median, 38 versus 21 months) compared with those who did not (P = .002). One hundred three patients (56%) were MRD negative on day 100 by 6- or 7-color flow cytometry. Patients achieving MRD negativity had a superior PFS (median, 26 versus 17 months; P < .001) and superior OS (5-year OS rate, 64% versus 41%; P = .023) compared with MRD-positive patients. In the subgroups with deletion(17p) (n = 84) and those with ≥2 HR cytogenetic abnormalities (n = 32), sCR and MRD negativity did not translate into a superior PFS or OS. In patients with t(4;14) (n = 65), sCR post-transplant led to a trend toward superior PFS and MRD negativity translated into significantly superior PFS and OS. Depth of response and MRD status are important surrogate markers for survival in patients with HR cytogenetics, except in the subgroups with deletion(17p) and ≥2 HR abnormalities, where sCR and MRD negativity post-transplant did not translate into a superior survival., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

We evaluated 1070 patients with newly diagnosed multiple myeloma, who completed a single line of induction therapy followed by autologous stem cell transplantation. Patients with pre-transplant <5% BMPC had a threefold likelihood of achieving stringent complete response (sCR) after transplant compared to those with BMPC ≥5% (45.6% vs. 16.3%; p < 0.0001). The median progression-free survival and overall survival from transplant for patients with pre-transplant BMPC <5% and ≥5% was 30.8 and 115.2 months compared to 20.8 and 74.1 months, respectively (p < 0.0001 for both comparisons). The effect of pre-transplant BMPC was most pronounced in patients achieving complete response or very good partial response after transplant. In conclusion, pre-transplant BMPC <5% is an important prognostic marker of long-term survival after transplant and should be routinely incorporated into pre-transplant risk stratification.

Autologous stem cell transplantation is an important part of therapy in patients with multiple myeloma. Some patients fail to collect the desired number of stem cells while others require multiple apheresis to reach the desired apheresis target. The aim of this study was to determine the predictive factors and if the hematopoietic kinetics of recovery were predictive for outcome of stem cell mobilization in cyclophosphamide + growth factor (CY-GF) mobilized patients. Three hundred and ninety six consecutive CY-GF mobilization attempts between January 2000 and December 2009 at Mayo Clinic, Rochester, MN were analyzed. Patients were divided into three groups: optimal (>5 × 10(6) CD34/kg), suboptimal (2-5 × 10(6) CD34/kg) and poor (<2 × 10(6) /kg CD34+ cells) mobilization groups. About 86% of patients had optimal stem cell collection, whereas 8% had suboptimal collection and 6% had poor (or failed) collections. Age, Hb, WBC, and platelet levels had an impact on mobilization results. Time to peripheral blood (PB) CD34+cells >10/μL predicted for efficiency of collection and the interval between recovery of WBC>1 post-CY to PB CD34+ cells>10 was shorter in the optimal collection groups. These findings suggest that for patients with a PB CD34+ cell count below 10/μL on Day 13 following CY or 1 day after the WBC>1 × 10(9) /L, addition of plerixafor may be helpful to salvage the mobilization attempt., (Copyright © 2011 Wiley Periodicals, Inc.)

Multiple myeloma (MM) remains an incurable illness affecting nearly 20,000 individuals in the United States per year. High-dose melphalan (HDM) with autologous hematopoietic stem cell support (ASCT) is one of the mainstays of therapy for younger patients, but little advancement has been made with regards to conditioning regimens. We opted to combine (153)Samarium ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP), a radiopharmaceutical approved for the palliation of pain caused by metastatic bone lesions, with HDM and ASCT in a Phase II study. Individualized doses of (153)Sm were based on dosimetry and were calculated to deliver 40 Gy to the bone marrow. The therapeutic dose of (153)Sm-EDTMP was followed by HDM and ASCT. Forty-six patients with newly diagnosed or relapsed disease were treated. Study patients were compared to 102 patients contemporaneously treated with HDM and ASCT. Fifty-nine percent of study patients achieved a very good partial response (VGPR) or better. With a median follow-up of 7.1 years, the median overall survival and progression free survival (PFS) from study registration was 6.2 years (95% CI 4.6-7.5 years) and 1.5 years (1.1-2.2 years), respectively, which compared favorably to contemporaneously treated non-study patients. Addition of high-dose (153)Sm-EDTMP to melphalan conditioning appears to be safe, well tolerated, and worthy of further study in the context of novel agents and in the Phase III setting., (2010 Wiley-Liss, Inc.)

Autologous stem cell transplantation as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, one-third to one-half of patients did not achieve partial response at transplantation. Previous medical literature has shown that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after high-dose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplantation. With the introduction of novel agents-immunomodulatory drugs and proteasome inhibitors-response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response (never responded or progressed during continuous therapy) after induction therapy with a regimen that contains thalidomide or lenalidomide. Unlike patients in reports published previously-before immunomodulatory drugs-patients who do not achieve partial remission have a significantly shorter overall survival from transplantation (73.5 vs 30.4 months) and a shorter progression-free survival (22.1 vs 13.1 months; P < .001). Absence of a response to induction therapy with thalidomide or lenalidomide predicts a poorer outcome after high-dose therapy.

We report on the feasibility of outpatient transplant in 716 patients undergoing autologous stem cell transplant for multiple myeloma at Mayo Clinic's site in Rochester, MN, from January 1, 2000, through October 31, 2007. We also report on the development and effect of a multidisciplinary quality initiative implemented by the Mayo Clinic Blood and Marrow Transplant Program involving physicians, nurses, pharmacists, dietitians, and financial specialists for outpatient management of patients undergoing stem cell transplant. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Analysis of hospitalization trends since inception of the program showed that 278 (39%) of the 716 patients treated completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization. We also assessed recent treatment-related mortality rates during a 33-month period after implementation of the program (between January 1, 2005, and October 1, 2007). The 100-day survival rate was 99.5% for patients with low-risk myeloma (transplant during first plateau; n=201) and 97.2% for patients with high-risk myeloma (refractory, relapsing or second or greater plateau; n=71). The overall 100-day survival rate was 98.9%. Our experience shows that outpatient transplant is feasible for all patients with multiple myeloma and results in shorter hospital stays and low treatment-related mortality rates.

High-dose chemotherapy for the management of immunoglobulin light chain amyloidosis remains an effective and viable treatment technique for selected patients with this disorder. We reviewed the medical records of 434 patients uniformly treated with high-dose chemotherapy and autologous stem cell transplant at Mayo Clinic, Rochester, Minnesota, between 8 March 1996 and 13 April 2010. Outcomes, engraftment, and predictors of early mortality were reviewed. Median survival has not been reached for the patients with a complete response, is 107 months for those with a partial response, and is 32 months for patients with no response ( p < 0.001). The only predictor of survival was cardiac stage ( p < 0.001). The hematologic response rate is predictive for organ response rates. Both hematologic and organ responses are associated with improved survival. [ABSTRACT FROM AUTHOR]

Highlights • Autologous stem cell transplantation can be safely performed in carefully selected patients aged 70 or older. • The overall response rate is 75% in this cohort. • Progression-free and overall survival are encouraging for a population with competing risks for death. Abstract Autologous stem cell transplantation (ASCT) has been used in treatment for immunoglobulin light chain (AL) amyloidosis for over 2 decades and is generally reserved for patients younger than 70 years. Herein we report on outcomes of ASCT in a cohort of patients with AL amyloidosis aged 70 years or older. Between August of 2002 and April of 2017, 34 patients aged 70 years or older, with biopsy-proven AL amyloidosis, received an ASCT at the Mayo Clinic Rochester. Seventy percent of patients (n = 24) were transplanted within 6 months of diagnosis, and 74% (n = 25) received reduced-intensity conditioning with melphalan <200 mg/m2. Sixty-five percent of patients (n = 22) required hospitalization with a median duration of hospital admission of 8 days. Common reasons for hospitalization included fever or infection (14%), cardiac arrhythmia (14%), nutritional support (24%), and volume overload (19%). Overall response rate was 75%, with a complete response seen in 25% of patients. Overall survival and progression-free survival for the cohort were 66 months and 40 months, respectively. One patient died within 100 days of transplant, representing a 3% 100-day mortality rate. ASCT is safe and efficacious in carefully screened patients aged 70 or above. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) is the standard-of-care for fit/younger patients with multiple myeloma. Outcomes are heterogeneous for those achieving less than a complete response (CR) after transplant; novel predictors of early relapse are needed to guide consolidation, maintenance and disease monitoring strategies. The post-ASCT proliferative index of clonal plasma cells (cPC) predicts for survival.1 In the present study, we evaluated nonmalignant proliferating polyclonal plasma cells (pPC) for an independent effect on outcome. From January 1 2013 to January 1 2014, 176 consecutive patients with multiple myeloma underwent their first ASCT at our institution and had a bone marrow (BM) specimen collected approximately 100 days post-ASCT. All BM was subject to multi-parametric flow cytometry using a BD FACS Canto IITM as previously described. Briefly, proliferating (S-phase) pPC were classified using DAPI staining and reported as a percentage of total pPC, which was calculated if there were at least 150 pPC/500000 events (Figure 1). Those with less than 150 pPC were deemed "non-evaluable." Time to next therapy (TNT) was calculated from ASCT Day 0 to the initiation of a new therapy (not including maintenance or consolidation), with patients censored at time of last follow-up or death without further therapy. Overall survival (OS) was calculated from Day 0 to death, with living patients censored at time of last follow-up. Statistics were performed using R 3.5.2. Responses at Day 100 were as follows: 71 (40%) CR, 48 (27%) very good partial response, 57 (33%) partial response or less. Among the 77 of 105 (73%) patients with

Primary (1°) and secondary (2°) graft failure are a rare but serious complication in autologous stem cell transplant (ASCT) for multiple myeloma (MM) for which reinfusion of cryopreserved autologous stem cells (i.e. stem cell boost) can be performed in the absence of conditioning chemotherapy. However, the efficacy of this approach and kinetics of engraftment without conditioning chemotherapy is unknown. Retrospective analysis was performed of all patients (pts) with MM who experienced 1°graft failure (absence of initial donor cell engraftment with peripheral blood ANC <0.5 × 109/L and platelets <20 × 10 9/L by day +21) or 2°graft failure (initial engraftment and subsequent loss of graft with decrease in ANC to <0.5 × 109/L and platelets <20 × 109/L) after ASCT. We looked at pts who received a stem cell (SC) boost without conditioning chemotherapy and abstracted pre-transplant laboratory data, SC engraftment kinetics and pertinent clinical findings from the EMR. Between 1/1/2003 and 9/30/2018, 21 pts received SC boosts; 18 patients met inclusion criteria. At time of ASCT, median age was 62 years (range: 44-74); 56% female, median neutrophil count was 3.96 × 109/L (IQR 2.5–4.6), median platelet count was 226 × 109/L (IQR 194-380) and bone marrow evaluations demonstrated no dysplasia or atypical genetics. 9 pts were mobilized with growth factor only (i.e. G-CSF); 8 received chemomobilization (G-CSF & cyclophosphamide), 2 pts required Plerixifor and median apheresis sessions was 2 (range 1-6). Most pts collected ≥3 × 106 SC in 1 apheresis. Median time from SC collection to ASCT was 8 days (IQR 6-18) for upfront ASCT pts (n=15) and in delayed ASCT pts (n=3), the range was 214 to 3205 days. 16 pts (90%) had high dose melphalan only conditioning, 1 pt had Ibritumomab tiuxetan and another had 153-Samarium-EDTMP added to high dose melphalan. The median ASCT dose was 4.63 × 106 cells/kg (IQR 3.7-6.51). SC boost details are described in table 1. There was no association between neutrophil or platelet count at mobilization or SC dose with engraftment failure by χ2 analysis. This is the only report on the kinetics and outcomes for stem cell boost without conditioning chemotherapy in MM following 1° or 2° graft failure. All pts engrafted both platelets and/or neutrophils soon after SC boost providing evidence that this is an effective procedure in management of patients with either 1° or 2° autologous graft failure. [ABSTRACT FROM AUTHOR]