Search

Hematologic response has emerged as a powerful prognostic factor for survival in patients with immunoglobulin light chain (AL) amyloidosis. Patients achieving a complete response (CR), based on serum and urine analysis, survive longest. However, data regarding the impact of bone marrow features post-therapy on response and survival are limited. We evaluated the impact of achieving a stringent CR (sCR), defined as undetectable bone marrow clonal plasma cells by flow cytometry, in patients with AL amyloidosis receiving an autologous stem cell transplant. A total of 573 consecutive patients transplanted for AL amyloidosis at the Mayo Clinic between April 2002 and August 2016 were included in the analysis. Of 540 patients in whom response was assessable, 220 patients (41%) achieved a CR, of whom 212 (96%) had a bone marrow biopsy at time of response assessment and were further analyzed for determination of sCR; 166 patients (78%) with a CR achieved an sCR, representing 31% of the whole cohort. Patients achieving a CR had a higher median percentage of bone marrow plasma cells (10% for CR versus 6% for sCR, P = .03), more patients with bone marrow plasma cells ≥ 10% (50% for CR versus 33% for sCR, P = .04), and were less likely to receive chemotherapy before transplantation (30% for CR versus 49% for sCR, P = .03) compared with those achieving sCR. Median overall survival for all patients achieving a CR was 175 months and was not statistically different between those achieving an sCR compared with those achieving a CR only (median not reached for sCR versus 175 months for CR, P = .65). Progression-free survival, however, was significantly shorter in patients failing to achieve an sCR (151 months for sCR versus 72 months for CR, P = .0003). Bone marrow examination post-transplant in AL amyloidosis is important and identifies patients who fail to achieve an sCR and progress earlier., (Copyright © 2018. Published by Elsevier Inc.)

Background: Matching at the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci is important in donor selection for patients undergoing unrelated allogeneic hematopoietic stem cell transplantation (ASCT). Additional matching across the MHC gamma region may further improve outcomes., Methods: The MHC gamma region was retrospectively genotyped in 66 adult recipients of ASCT and their 10/10 matched unrelated donors. A chart review was performed to determine whether MHC gamma matching impacted survival, relapse, or graft-versus-host disease., Results: Of 66 donor-recipient pairs, 26(39.4%) were gamma-type matches, 34(51.5%) were mismatches, and 6(9.1%) were "indeterminate." Matching status was not associated with overall survival (p = 0.43), relapse (p = 0.21), acute GVHD (p = 0.43), severe aGVHD (p = 0.31), or chronic GVHD (p = 0.23) in univariate analyses, nor in multivariate analyses (p = 0.28, 0.13, 0.29, 0.16, and 0.67, respectively), with or without adjusting for HLA-DPB1 matching status., Conclusions: In our single institution study, gamma-type matching status was not associated with outcomes of adult ASCT recipients., (Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Purpose Autologous stem-cell transplantation (ASCT) has been used in patients with immunoglobulin light chain (AL) amyloidosis for more than two decades. Early experience raised concerns regarding safety with high early-mortality rates. Patients and Methods We report 20 years of experience with ASCT for AL amyloidosis at the Mayo Clinic Rochester. In all, 672 consecutive patients receiving ASCT for AL amyloidosis were divided into three cohorts on the basis of date of transplantation (cohort 1, 1996-2002 [n = 124]; cohort 2, 2003-2009 [n = 302]; and cohort 3, 2010-2016 [n = 246]). Results The median age for the entire cohort was 59 years, with patients in cohort 3 being slightly older than those in the other two cohorts (60 v 58 v 54 years for cohorts 3, 2, and 1, respectively; P < .001). Fewer patients in cohort 3 had more than two organs involved (9% v 18% v 19% for cohorts 3, 2, and 1, respectively; P < .001). More patients received pretransplantation therapy in cohort 3 compared with earlier time periods (49% v 38% v 42% for cohorts 3, 2, and 1, respectively; P = .02). Hematologic response was higher in cohort 3 (84% v 79% v 69% for cohorts 3, 2, and 1, respectively; P = .002). Median overall survival for the entire cohort was 122 months and improved over time (not reached v 120 months v 75 months for cohorts 3, 2, and 1, respectively; P < .001). Treatment-related mortality declined over time (2.4% v 8.6% v 14.5% for cohorts 3, 2, and 1, respectively; P < .001). On multivariable analysis, conditioning dose, Mayo stage 2012, and hematologic response were independent predictors of survival. Conclusion ASCT is a highly effective therapy for AL amyloidosis. The improved survival and markedly reduced treatment-related mortality in eligible patients indicate that this will remain an important first-line option even in the era of treatment approaches that use novel agents.

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.

Graft-mediated antileukemia (GVL) activity is a major factor contributing to the success of allogeneic hematopoietic stem transplantation (aHCT). Recent advances have permitted the establishment of GVL activity without the need for a myeloablative conditioning regimen, thereby permitting even older and sicker patients to avail of potentially curative therapy. Use of adoptive immunotherapy by combining reduced intensity conditioning and donor leukocyte infusion (DLI) has resulted in strategies that can be exploited to maximize GVL effects while minimizing toxicity. These advances, combined with new molecularly targeted agents, creates new possibilities to develop less toxic, curative therapy for a greater number of patients. This review summarizes pertinent information regarding the evidence in favor of GVL effects, the impact of disease type and mechanisms of GVL.

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870–0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828–0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782–0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831–0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To evaluate the impact of killer immunoglobulin-like receptor (KIR) genotyping in allogeneic hematopoietic stem cell transplantation for myeloid disorders at our institution, retrospective KIR genotyping was performed on 77 patients and their 10/10 matched unrelated donors. In a multivariate model including donor age, HLA-DPB1 permissiveness, and presence of donor KIR B/x, an association with overall survival was observed (p =.047). Within the model, increasing donor age increased risk (RR 1.03 [1.00–1.06]/year, p =.046), while donor KIR and HLA-DPB1 permissiveness were not associated with risk (RR 0.51 [0.26–1.03] and RR 0.68 [0.34–1.36]). Grouping recipients by conditioning regimen or limiting the analysis to recipients of peripheral blood stem cells, no association between donor KIR and survival or relapse was identified. No significant associations were observed between overall survival, relapse, grade III-IV acute, or chronic graft versus host disease and presence of KIR B (B/x), quantity of donor KIR B haplotype motifs, or centromeric KIR type (all p >.05). [ABSTRACT FROM AUTHOR]

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/m2 compared to 41 months in the 140 mg/m2 group (P < 0.0001). In conclusion, patients receiving novel therapy post ASCT and melphalan conditioning dosing at 200 mg/m2 at diagnosis had better outcomes. [ABSTRACT FROM AUTHOR]

Background: Neutropenia is a risk factor for development of infections; however, the direct effect of neutropenia on development of bloodstream infection (BSI) is not known. D‐index, which is area between the neutrophil time curve and a neutrophil count of 0.5 × 109/L, incorporates the combined effect of severity and duration of neutropenia. We aimed to evaluate whether D‐index can be used as a marker for BSI in patients with allogeneic stem cell transplantation. Method: We conducted a retrospective cohort study of patients undergoing allogeneic stem cell transplantation between January 1, 2005, and September 30, 2015. The primary outcome measure was the development of BSI within 30 days of transplantation. Results: A total of 714 patients were included in the study of whom 101 developed BSI. Patients with BSI had a significantly higher median D‐index value compared with patients who did not have BSI (4990 vs. 3570, P <.001). As a marker, the performance of the D‐index was similar to that of the duration of profound neutropenia (P =.18) and significantly better than the total duration of neutropenia (P =.001). Conclusion: The D‐index performed better than the total duration of neutropenia as a marker for BSI in patients with allogeneic stem cell transplantation. There was no difference between D‐index and, a more easily calculable indicator, duration of profound neutropenia. [ABSTRACT FROM AUTHOR]

Magnesium is an essential element that is involved in critical metabolic pathways. A diet deficient in magnesium is associated with an increased risk of developing cancer. Few studies have reported whether a serum magnesium level below the reference range (RR) is associated with prognosis in patients with diffuse large B cell lymphoma (DLBCL). Using a retrospective approach in DLBCL patients undergoing autologous stem cell transplant (AHSCT), we evaluated the association of hypomagnesemia with survival. Totally, 581 patients eligible for AHSCT with a serum magnesium level during the immediate pre-transplant period were identified and 14.1% (82/581) had hypomagnesemia. Hypomagnesemia was associated with an inferior event-free (EFS) and overall survival (OS) compared to patients with a serum magnesium level within RR; median EFS: 3.9 years (95% CI: 1.63–8.98 years) versus 6.29 years (95% CI: 4.73–8.95 years) with HR 1.63 (95% CI: 1.09–2.43, p = 0.017) for EFS, and median OS: 7.3 years (95% CI: 2.91—upper limit not estimable) versus 9.7 years (95% CI: 6.92–12.3 years) with HR 1.90 (95% CI: 1.22–2.96, p = 0.005) for OS months 0–12, respectively. These findings suggest a potentially actionable prognostic factor for patients with DLBCL undergoing AHSCT. [ABSTRACT FROM AUTHOR]

Summary: 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

The article discusses research which examined the adult and pediatric bone marrow failure syndrome database at the Mayo Clinic from 1990-2016 for patients with inherited bone marrow failure syndrome (IBMFS). Topics covered include the analysis of the electronic medical record for germline disorders, the demographic characteristics, clinical correlates, details on myeloid clonal evolution and outcomes, and outcomes of allogeneic stem cell transplantation.

Objective HLA- DPB1 matching may impact allogeneic hematopoietic stem cell transplantation ( ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA- DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. Methods Retrospective HLA- DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 loci (10/10). Using the ImMunoGeneTics/ HLA T-cell epitope matching algorithm, mismatch status was classified as permissive or non-permissive. Results Of 153 donor-recipient pairs, 22 (14.4%) were HLA- DPB1 matches, 64 (42.8%) permissive mismatches, and 67 (43.8%) non-permissive mismatches. DPB1 mismatch increased risk of chronic graft-versus-host disease ( cGVHD; RR 2.89 [1.19-9.53], P=.016) compared with DPB1-matched transplants, but there were no differences in overall mortality, risk of relapse, or acute GVHD ( aGVHD). Combining matches and permissive mismatches and comparing to non-permissive mismatches, there was no significant difference in overall survival or relapse; however, patients receiving non-permissive mismatched transplants experienced greater risk of aGVHD overall and severe aGVHD ( RR 1.66 [1.13-2.44], P=.010 and RR 1.97 [1.10-3.59], P=.024, respectively). Conclusion In this single-center study, HLA- DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (SCT) is a common management strategy for select patients with immunoglobulin light-chain amyloidosis, but no trials have documented improved overall survival.Methods: Eighty-nine patients with biopsy-proven immunoglobulin light-chain amyloidosis were allowed to select treatment with melphalan plus dexamethasone (n = 34) or SCT (n = 55); all patients were transplant eligible. Treatment preference resulted in imbalanced study arms. Patients who selected SCT were younger, more frequently had an Eastern Cooperative Oncology Group performance status score less than 2, had lower-stage amyloidosis, and had a lower incidence of cardiac amyloidosis.Results: Patients receiving melphalan plus dexamethasone had a 3-year progression-free survival rate of 29.1% and an overall survival rate of 58.8%. Patients undergoing SCT had a 3-year progression-free survival rate of 51.7% and an overall survival rate of 83.6%. An attempt to match patients between the 2 arms in terms of risk produced 24 matched triplet sets (2 SCT patients for each melphalan-dexamethasone patient); there was no difference in hematologic response, but there was better survival after autologous SCT. A propensity score-matched analysis of the cohorts (melphalan plus dexamethasone vs SCT) showed an overall mortality hazard ratio of 2.56 (P < .01).Conclusions: Although the study had limitations, similar hematologic responses and improved survival were observed after SCT versus melphalan plus dexamethasone. Cancer 2016;122:2197-205. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The current study was conducted to determine characteristics distinguishing the 10-year survivor group in patients with systemic immunoglobulin light chain (AL) amyloidosis who underwent autologous stem cell transplantation (SCT). METHODS: The study group included all 74 patients with AL amyloidosis who underwent high-dose melphalan treatment supported by autologous SCT since the beginning of the Mayo Clinic's SCT program until prior to August 2001. RESULTS: A total of 32 patients (43%) patients survived for > 10 years. Statistically significant baseline differences in the 10-year survivor group included: 1) the number of organs involved; 2) septal thickness; 3) total cholesterol; and 4) urine total protein. The number of organs involved was the only predictor found on multivariable analysis. Depth of the response to therapy, as measured by the lowest posttransplantation serum free light chain level, was found to be the most significant indicator of durability of response. CONCLUSIONS: Autologous SCT can offer durable benefit for patients with AL amyloidosis. The number of organs involved offers the greatest pretreatment prognostic value, whereas the lowest posttransplantation serum free light chain level offers the best posttreatment prognostic value. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) represent a heterogeneous population of stromal cells with pluripotent mesenchymal differentiation potential. They have been found to have immunosuppressive properties and the ability to modulate angiogenesis and endogenous tissue repair by in vitro and animal studies. Clinical trials have examined the utility of these cells in autoimmune and inflammatory conditions. In particular, in allogeneic hematopoietic stem cell transplant (HSCT), multiple studies have been conducted to explore the use of MSC to treat acute and chronic graft-versus-host disease (GVHD) and for cotransplantation with HSCT to promote HSC engraftment and prevent GVHD. We review here the results of these studies and discuss some challenges of this treatment modality in this disease setting. [ABSTRACT FROM AUTHOR]

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]

Major recent advances in understanding the biology of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) have improved clinical evaluation and influenced treatment decisions. CLL can be diagnosed early and accurately, and biological measurements can be used to predict a prognosis at diagnosis. Individual patient care can be risk stratified to optimize benefit and minimize complications of therapy. Purine analogs and monoclonal antibodies have markedly improved the efficacy of initial therapy but are not curative. The treatment of relapsed and refractory CLL is less successful. However, recent developments suggest that allogeneic stem cell transplant could have a larger role in a selected group of these patients. Potential new treatment modalities include targeted molecules that interrupt key components of CLL cell survival pathways, and active and passive immunotherapy. The management of CLL is in a dynamic phase of rapid evolution. Risk stratification using biological prognostic markers can improve current patient care and direct future clinical research. [ABSTRACT FROM AUTHOR]

Background Scleromyxedema is a rare chronic fibromucinous disorder that can have devastating clinical manifestations, including sclerosis of the skin with progressive pharyngeal and upper airway involvement, resulting in high mortality due to respiratory complications. Herein we describe a novel therapeutic approach. Because autologous hematopoietic stem cell transplantation is effective in other plasma cell proliferative disorders, it may be effective in this setting. Observations We retrospectively evaluated 6 patients who were offered high-dose chemotherapy with stem cell rescue as treatment for scleromyxedema. One heavily pretreated patient was unable to mobilize stem cells. The remaining 5 patients mobilized stem cells and underwent successful transplantation. There was no treatment-related mortality. Hematologic responses were seen in 4 patients, including 2 complete remissions and 2 partial remissions, and all 4 had improvement in extracutaneous manifestations. All 4 patients subsequently had relapse of the monoclonal protein, and 3 developed skin relapses at 14, 37, and 45 months. Conclusions High-dose chemotherapy with stem cell rescue is feasible for patients with scleromyxedema and, although not curative, offers durable remission in most patients. This therapy should be considered before treatment with alkylating agents or other treatments that could adversely affect the ability to collect stem cells. [ABSTRACT FROM AUTHOR]

The author comments on research appearing within this issue of the journal concerning allogeneic hematopoietic stem cell transplantion (AHCT) for the treatment of chronic lymphocytic leukemia (CLL) and small lympocytic lymphoma. Particular attention is paid to the study "Long-term toxicity of allogeneic stem cell transplantation in fludarabine-refractory chronic lymphocytic leukemia." The author argues that AHCT may not be suitable for the majority of patients with CLL.

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/m2 (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/m2 (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. [ABSTRACT FROM AUTHOR]

• The high prevalence and severity of cardiac involvement are the main drivers for the poor outcome in patients who have 3 or more organs involved. • An NT-proBNP level of ≥2000 pg/mL was an independent predictor for shorter progression-free and overall survival. • Patients with ≥3 organs involved who have minimal cardiac involvement have good outcomes with ASCT and should be considered transplant eligible. Prior reports have suggested that 3 or more organs involved is a contraindication for autologous stem cell transplant (ASCT) in amyloid light chain (AL) amyloidosis. Therefore, most centers limit transplantation to patients who have no more than 2 organs significantly involved. We retrospectively reviewed all patients with AL amyloidosis with ≥3 involved organs and who had ASCT between 1996 and 2015 at Mayo Clinic, Rochester, Minnesota to assess transplant safety and outcomes. Seventy-five patients with ≥3 organs involved underwent ASCT. Median age at diagnosis was 54 years, and 67% were men. The heart was involved in 95%, followed by the kidneys (84%). Thirty-eight patients (51%) had no induction treatment before ASCT. Full-dose melphalan (200 mg/m2) was given in 45%, and the remainder received 140 mg/m2. Overall hematologic response rate was 75%. The median progression-free survival (PFS) and overall survival (OS) were 16 and 68 months, respectively. The 100-day mortality was 16%, and 44 patients (59%) died during follow-up. The most common causes of death were cardiovascular events (32%) and progressive amyloidosis (25%). On multivariable analysis, predictors for PFS were Mayo 2012 stage III/IV (relative risk [RR], 3.3; P =.0012) and hematologic response (at least very good partial response; RR,.4; P =.012). An N-terminal pro–brain natriuretic peptide (NT-proBNP) level of ≥2000 pg/mL was an independent predictor for shorter PFS (RR, 2.6; P =.013). Predictors for OS included any hematologic response (RR,.12; P =.0015), melphalan 200 mg/m2 (RR,.2; P =.014), and Mayo 2012 stage III/IV (RR, 7.7; P =.0002). An NT-proBNP level ≥ 2000 pg/mL was a powerful predictor of OS (RR, 4; P =.013). The number of organs involved (3 versus >3) did not significantly impact PFS or OS. We conclude that the high prevalence and severity of cardiac involvement are the main drivers for the poor outcome in patients who have ≥3 organs involved. Using selection criteria defined for safe transplantation in cardiac amyloidosis should result in low therapy-related mortality independent of the number of organs involved. The severity of cardiac involvement should be the major criterion for transplanting patients with AL amyloidosis that have ≥3 organs involved and not merely the number of organs involved. [ABSTRACT FROM AUTHOR]

Highlights • Autologous stem cell transplant is efficacious in patients with IgM-related AL amyloidosis. • A hematologic response is seen in approximately 90% of patients, with 76% of patients achieving at least a very good partial response. • Organ response is seen in approximately 60% of patients and predicts both progression-free and overall survival. Abstract IgM-related amyloid light-chain (AL) amyloidosis is a rare disease, with patients presenting with more renal and neurologic involvement and less cardiac involvement compared with those with non–IgM-related disease. We retrospectively reviewed 38 patients receiving autologous stem cell transplant (ASCT) for IgM-related AL amyloidosis at the Mayo Clinic between May 1999 and June 2018. Median age was 61years, and 71% were men. The most common organs involved were renal (63%), neurologic (32%), and cardiac (26%). The median difference between involved and uninvolved free light chains was 6.2mg/dL, and most patients had early Mayo stage disease (87% Mayo stage I 2004 and 74% Mayo stage I 2012). The overall response rate was 92%, with 76% of patients achieving at least a very good partial response. Renal response was seen in 65% of patients (15/23; median time, 18 months post-ASCT; range 3 to 52) and cardiac response in 60% of patients (6/10; median time, 12 months post-ASCT; range 10 to 35). Median progression-free survival (PFS) and overall survival (OS) was 48 and 106 months, respectively. Organ response predicted better PFS and OS (median PFS, 93 months for organ response versus 16 months for no organ response [ P =.0006]; and median OS, 123 months for organ response versus 41 months for no organ response [ P =.02]). Two patients died within 100days of transplant, representing a 5% 100-day mortality. ASCT is an effective therapy that can be safely delivered to carefully selected patients with IgM-related AL amyloidosis. [ABSTRACT FROM AUTHOR]

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. [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]

Abstract: Historically, up to 30% of patients were unable to collect adequate numbers of peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (ASCT). Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has shown superior results in mobilizing peripheral blood (PB) CD34+ cells in comparison to G-CSF alone, but its high cost limits general use. We developed and evaluated risk-adapted algorithms for optimal utilization of plerixafor. In plerixafor-1, PBSC mobilization was commenced with G-CSF alone, and if PB CD34 on day 4 or day 5 was <10/μL, plerixafor was administered in the evening, and apheresis commenced the next day. In addition, if on any day, the daily yield was <0.5 × 106 CD34/kg, plerixafor was added. Subsequently, the algorithm was revised (plerixafor-2) with lower thresholds. If day-4 PB CD34 <10/μL for single or <20/μL for multiple transplantations, or day-1 yield was <1.5 × 106 CD34/kg, or any subsequent daily yield was <0.5 × 106 CD34/kg, plerixafor was added. Three time periods were analyzed for results and associated costs: January to December 2008 (baseline cohort; 319 mobilization attempts in 278 patients); February to November 2009 (plerixafor-1; 221 mobilization attempts in 216 patients); and December 2009 to June 2010 (plerixafor-2; 100 mobilization attempts in 98 patients). Plerixafor-2 shows a significant improvement in PB CD34 collection, increased number of patients reaching minimum and optimal goals, fewer days of apheresis, and fewer days of mobilization/collection, albeit at increased costs. In conclusion, although the earlier identification of ineffective PBSC mobilization and initiation of plerixafor (plerixafor-2) increases the per-patient costs of PBSC mobilization, failure rates, days of apheresis, and total days of mobilization/collection are lower. [Copyright &y& Elsevier]

High Dose Melphalan (HDM) and stem cell transplantation is an effective treatment for AL amyloidosis, but is associated with high treatment related mortality in those with cardiac involvement. We studied 187 patients with AL and cardiac involvement who underwent HDM at our institution between May 1996 and September 2008. The median age was 57 years and median time to HDM from diagnosis was 3.6 months. Half of the patients received reduced dose melphalan (100-160 mg/m2). The median OS was 66 months and 54 months from diagnosis and HDM respectively, and 91 (49%) patients were alive at last follow up; 52 months (median) from HDM. Thirty patients (16%) died within 100 days of transplant; only low serum albumin predicted early deaths. Overall, hematologic and cardiac responses were seen in 66% and 41%, respectively. The median OS for patients with and without a hematologic response was not reached (NR) and 22 months, respectively (P<0.01), and with and without any decrease in NT-ProBNP was NR and 26 months, respectively (P<0.01). In multivariate analysis of baseline factors, only reduced dose melphalan predicted shorter OS. HDM is feasible in patients with cardiac amyloidosis, and achievement of hematologic and organ response is associated with improved survival. [ABSTRACT FROM AUTHOR]

Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease-free survival (DSF) after allogeneic hematopoietic cell transplantation (HCT). In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range: 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA nonidentical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day treatment-related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Corresponding 5-year overall survival (OS) rates were 37%, 30%, and 40%, respectively. DFS rates were 33%, 27%, and 22%, respectively. DFS for patients receiving reduced-intensity transplants was comparable: 39% for HLA identical sibling donors and 17% for unrelated donors at 3 years. In this large retrospective series, allogeneic transplantation for myelofibrosis resulted in long-term relapse-free survival (RFS) in about one-third of patients. [Copyright &y& Elsevier]

A specific predictor during routine follow-up to ascertain risk for postautologous peripheral blood hematopoietic stem cell transplantation (post-APHSCT) relapse in non-Hodgkin lymphoma (NHL) has not been identified. Thus, we studied if new-onset lymphopenia measured by the absolute lymphocyte count (ALC) was a marker of post-APHSCT NHL relapse. ALC was obtained at the time of confirmed relapse, and at last follow-up with no relapse. From 1993 until 2005, 269 patients treated with APHSCT for diffuse large B-cell lymphoma (DLBCL) were included in this study. Patients at last follow-up without relapse (N=137) had a higher ALC compared with those with low ALC at the time of confirmed relapsed (N=132) (median ALC ×109/L of 1.66 versus 0.71, P < .0001, respectively). ALC at follow-up was a strong predictor for relapse with an area under the curve (AUC)=0.86 (P < .0001). An ALC <1.0×109/L at the time of confirmed relapse had a positive predictive value of 89% and a positive likelihood ratio of 8.4 to predict relapse post-APHSCT. Patients with an ALC ≥1.0×109/L (N=147) had a cumulative incidence of relapse of 19% versus 92%, with an ALC <1.0×109/L (N=122) (P < .0001). This study suggests that new-onset lymphopenia measured by ALC can be used as marker to assess risk of DLBCL relapse during routine follow-up for after APHSCT. [Copyright &y& Elsevier]

Introduction There have been considerable advances in the understanding of molecular markers in acute myeloid leukemia(AML). It is widely accepted that internal tandem duplication (ITD) in the juxta membrane domain of the fms-like tyrosine kinase-3 (FLT3) gene in patients with AML is associated with an increased risk of relapse and reduced overall survival. In several studies, alloSCT performed in first complete remission (CR) from matched-related donors (MRDs) has been shown to result in an improved survival. There is also evidence that alloSCT improves OS in high allelic ratio FLT3-ITD AML and in patients with low allelic ratio FLT3-ITD AML and wild-type nucleophosmin (NPM1) but not in mutated NPM1 with low FLT3 ITD ratio. We wanted to validate these findings in our own cohort. Methods We retrospectively reviewed 723 consecutive patients (>18 years) with newly diagnosed AML treated at Mayo clinic between January 2007 and July 2016. Patients with intermediate-risk cytogenetics and known NPM1 and FLT3 molecular genetics were included in the study (n =198). Patients who had M3 AML, who were lost to follow up and without molecular data were excluded. We analyzed outcomes based on therapy and molecular mutations. Results Baseline characteristics are listed in Table 1. As expected patients receiving alloSCT were younger and a higher proportion received high intensity induction therapy. The majority of patients were transplanted in CR 1 (72%, n=55), Table 2. Median time to transplant was 4.6 months (range 2-64 months). Median follow up for the entire cohort was 62 months. At last follow up 117 (59%) of patients have died. Median OS for the whole cohort was 27 months. OS was longer in patients receiving alloSCT (median OS 87 months vs 16 months for No SCT, p=0.0001)(Figure 1A). This survival advantage remained significant amongst patients achieving CR1 (Figure 1B). Molecular mutations predicted survival based on FLT3 and NMP1 status primarily amongst the non-transplant cohort (Figure 1C). Patients receiving SCT had a similar survival irrespective of molecular mutation profile(Figure 1D). Amongst the FLT3+ cohort, data on subtype and ITD allelic ratio were available in 47 patients (FLT3 ITD low allelic ratio (<0.5), n=13, FLT3 ITD high allelic ratio (≥0.5), n=26 and FLT3 TKD, n=8). Patients with a high allelic ratio FLT3 ITD mutation appeared to have the worst survival, although this did not meet statistical significance (median OS 69 months for FLT3 ITD low vs 21 months for FLT3 ITD high, p=0.16). Conclusion In our cohort, patients with intermediate risk AML achieving CR1 benefited from alloSCT. The poor prognostic impact of FLT3 mutations in this cohort may be abrogated by alloSCT. The FLT3 mutation burden (allelic ratio) may help further prognosticate this category of patients with intermediate risk AML. [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]

Background Melphalan (Mel) as a single agent is the most common conditioning regimen prior to autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Incorporation of other drug classes such as proteasome inhibitors (PI) as part of initial therapy or for treatment of relapsed disease has significantly improved outcomes in MM. Based on initial data showing synergy between PI and alkylating agents, we designed this trial to examine if adding carfilzomib (Cfz) to Mel would improve the efficacy of the conditioning therapy. Patients and Methods Patients with MM, undergoing a single, early transplant (≤12 months from diagnosis) were included provided they were eligible for full dose Mel conditioning. Escalating doses of Cfz (27, 36, 45, 56 mg/m2) were administered days -6, -5, -2, -1 with Mel (200 mg/m2) administered in two divided doses on days -4, -3. Stem cells were infused day 0. The phase 1 portion of the trial used a 3+3 dose escalation of Cfz. Responses were assessed using IMWG consensus response criteria. Results 49 patients were enrolled (Table 1). At median follow up of 12.9 months (0.4-48.4), 45 (91.8%) were alive; 41 (83.7%) were without progression. Responses outlined in Table 2. Median PFS from registration was 48.2 mos (95% CI; 21.3-NA). The 1 & 2-year PFS rates were 88.2% (70.5-95.5%) and 71.0% (45.9-86.1%), respectively. Overall, 6 patients had ≥ 1 dose of Cfz omitted (elevated creatinine-3, and 1 patient each with sinus bradycardia, pulmonary edema with atrial fibrillation and rapid ventricular response, and pathologic fracture requiring surgery). A ≥grade 3 hematological or non-hematological toxicity, regardless of attribution, occurred in 94% and 76%, respectively. ≥Grade 3 non-hematological toxicities seen in >1 patient are shown in Figure 1. Conclusion Adding Cfz to Mel as conditioning therapy for ASCT in MM is feasible/safe. Response rates and PFS are comparable to those seen in recent phase 3 trials. [ABSTRACT FROM AUTHOR]