Ciprofloxacin Versus Levofloxacin Prophylaxis in Hematopoietic Stem Cell Transplantation: A Randomized Trial.

OBJECTIVES: We aimed to assess whether there is a difference between ciprofloxacin and levofloxacin as prophylaxis in hematopoietic stem cell transplant (SCT) recipients. METHODS: This is a prospective, randomized trial in patients receiving SCT at Henry Ford Health in the United States of America. We randomly assigned patients (1:1) to receive ciprofloxacin or levofloxacin. The primary outcome was incidence of bloodstream bacterial infections (BSI) up to day 60 after SCT. RESULTS: Between June 4, 2018, and May 23, 2022, we randomly assigned 308 consecutive patients to receive ciprofloxacin (154 patients) or levofloxacin (154 patients). BSI was similar in both the ciprofloxacin and levofloxacin groups (18 [11.7%] vs 18 [11.7%]). Pneumonia was more frequent in the ciprofloxacin group compared to the levofloxacin group (18 [18%] vs 7 [23%]; relative risk 2.57, 95% CI 1.11-5.98; p = 0.028). There were no differences in neutrophil engraftment, fever, Clostridium difficile infection, relapse incidence, overall survival, non-relapse mortality, length of stay post-SCT, or intensive care unit admission. CONCLUSIONS: Although both prophylaxis regimens demonstrated the same efficacy in SCT recipients, levofloxacin prophylaxis led to less pneumonia in the first 60 days post-SCT. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03850379.

Acute patient-reported outcomes in B-cell malignancies treated with axicabtagene ciloleucel.

Chimeric antigen receptor T-cell therapy with axicabtagene ciloleucel (axi-cel) has considerably improved survival in adults with relapsed/refractory large B-cell lymphoma. This study reports patient-reported outcomes (PROs) such as quality of life (QOL) and toxicity in the first 90 days after treatment. Hematologic cancer patients treated with axi-cel (N = 103, mean age = 61, 39% female) completed SF-36 or PROMIS-29 QOL questionnaires prior to treatment and 90 days after. PRO-Common Terminology Criteria for Adverse Events toxicity items were completed by patients at baseline and 14, 30, 60, and 90 days after treatment. Mixed models examined change in PROs over time. From preinfusion to 90 days later, patients reported improvements in physical functioning, pain, and fatigue (ps < 0.01), but worsening of anxiety (p = 0.02). Patient-reported toxicities worsened by day 14 with improvement thereafter. The five most severe symptoms at day 14 included fatigue, decreased appetite, dry mouth, diarrhea frequency, and problems with concentration. Results indicate improvement in some domains of QOL over time with transient patient-reported toxicities.

Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT).

SWOG S0777, a randomized phase III trial, compared bortezomib, lenalidomide and dexamethasone (VRd) with lenalidomide and dexamethasone (Rd). This updated analysis includes 460 patients evaluable for survival endpoints: 225 eligible and analyzable patients were randomized to Rd and 235 to VRd. The 6-month induction was six 28-day cycles of Rd and eight 21-day cycles of VRd followed by Rd maintenance for all patients. Median follow up is 84 months. Median PFS is 41 months for VRd and 29 months for Rd: stratified hazard ratio (96% Wald Confidence Interval) was 0.742 (0.594, 0.928) and one-sided stratified log-rank P-value 0.003. Median OS for VRd is still not reached with median OS for Rd being 69 months: stratified hazard ratio (96% Wald Confidence Interval) was 0.709 (0.543, 0.926) and stratified two-sided P-value was 0.0114. Both PFS and OS were improved with VRd versus Rd adjusting for age (P-values: 0.013 [PFS]; 0.033 [OS])). Median duration of Rd maintenance was 17.1 months. The addition of bortezomib to lenalidomide dexamethasone for induction therapy results in a statistically significant and clinically meaningful improvement in PFS as well as better OS. VRd continues to represent an appropriate standard of care irrespective of age.

Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma.

PURPOSE: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits. PATIENTS AND METHODS: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m2; arm 1) to high-dose carfilzomib (56 mg/m2; arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory multiple myeloma with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on arm 1 could cross-over to arm 2 after progression on treatment. RESULTS: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (P = 0.113). Also, neither the median PFS [5 months and 8 months, respectively; HR, 1.061; 80% Wald confidence interval (CI), 0.821-1.370; P = 0.384] nor the median overall survival were significantly different (26 and 22 months, respectively; HR, 1.149, 80% Wald CI, 0.841-.571; P = 0.284). Sixteen patients crossed over to arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in arm 2, including fatigue, thrombocytopenia, and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs. CONCLUSIONS: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m2 dosing of carfilzomib over the 27 mg/m2 dose for the treatment of relapsed and/or refractory multiple myeloma. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.

Collection of Peripheral Blood Progenitor Cells in 1 Day Is Associated with Decreased Donor Toxicity Compared to 2 Days in Unrelated Donors.

Peripheral blood stem cells (PBSCs) have been increasingly used for allogeneic hematopoietic cell transplantation instead of bone marrow stem cells. Current National Marrow Donor Program policy recommends 5 days of daily filgrastim, followed by either 1 or 2 days of apheresis for unrelated donors, depending on collection center choice. To date, there are no published studies comparing the differences in donor experience between 1 day and 2 days of apheresis. We examined 22,348 adult unrelated donor collections in 184 centers between 2006 and 2016. Of these 22,348 donors, 20,004 (89.5%) had collection on 1 day, and the other 2344 (9.5%) had collection over 2 days. Information on why donors underwent apheresis in 1 day or 2 days was not available. Donors who underwent apheresis in 1 day were more likely to be male (67% versus 46%; P < .001), younger (age <30 years, 48% versus 36%; P < .001), and have a higher body weight (83.0 kg versus 75.9 kg; P< .001) and body mass index (BMI; >30, 30% versus 22%; P < .001). Successful collection of the requested CD34+ cell count was achieved on the first day in 82% of 1-day collections and in 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34+ cells/L in the product was higher on the second day of apheresis compared with the first day (23.8 × 106 CD34+/L on day 1 versus 28.7 × 106 CD34+/L on day 2; P< .001). Donors who underwent collection in 1 day were less likely to experience citrate toxicity (36% versus 52%; P< .001), hospitalization (1% versus 6%; P< .001), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% versus 26%; P < .001). Female sex, older age, collection via central lines, and higher BMI were factors associated with greater likelihood for the development of toxicity, whereas less toxicity was noted in those with higher CD34+ counts and more blood processed on the first day of collection. We conclude that although unrelated donors can be successfully collected in 1 day or 2 days, 1-day apheresis procedures were associated with less overall toxicity, and thus we recommend single-day collections, especially if the requested number of cells have been collected in 1 day.

Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse.

The phase 3 AETHERA trial established brentuximab vedotin (BV) as a consolidative treatment option for adult patients with classical Hodgkin lymphoma (cHL) at high risk of relapse or progression after autologous hematopoietic stem-cell transplantation (auto-HSCT). Results showed that BV significantly improved progression-free survival (PFS) vs placebo plus best supportive care alone. At 5-year follow-up, BV continued to provide patients with sustained PFS benefit; 5-year PFS was 59% (95% confidence interval [CI], 51-66) with BV vs 41% (95% CI, 33-49) with placebo (hazard ratio [HR], 0.521; 95% CI, 0.379-0.717). Similarly, patients with ≥2 risk factors in the BV arm experienced significantly higher PFS at 5 years than patients in the placebo arm (HR, 0.424; 95% CI, 0.302-0.596). Upfront consolidation with BV significantly delayed time to second subsequent therapy, an indicator of ongoing disease control, vs placebo. Peripheral neuropathy, the most common adverse event in patients receiving BV, continued to improve and/or resolve in 90% of patients. In summary, consolidation with BV in adult patients with cHL at high risk of relapse or progression after auto-HSCT confers a sustained PFS benefit and is safe and well tolerated. Physicians should consider each patient's HL risk factor profile when making treatment decisions. This trial was registered at www.clinicaltrials.gov as #NCT01100502.

Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma.

BACKGROUND: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n = 916), non-Hodgkin lymphoma (NHL; n = 3546) and plasma cell myeloma (PCM; n = 4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS. RESULTS: 335 MDS/AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR = 4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR = 2.5 [1.1, 2.5]); (2) ≥3 versus 1 line of chemotherapy for NHL (HR = 1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR = 2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort. CONCLUSIONS: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.

Safety Analysis of Brentuximab Vedotin from the Phase III AETHERA Trial in Hodgkin Lymphoma in the Post-Transplant Consolidation Setting.

The phase III AETHERA trial demonstrated the efficacy of brentuximab vedotin (BV) as consolidation therapy in patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression after autologous hematopoietic stem cell transplantation (auto-HSCT; hazard ratio, .57; P < .001). The objective of this analysis is to provide further detail on the most common and clinically important treatment-emergent adverse events (AEs) in the AETHERA BV arm including their occurrence and management. AEs of clinical importance occurring in patients who participated in AETHERA (BV + best supportive care [BSC], n = 165; placebo + BSC, n = 164) were evaluated for time to onset, manageability through dose modification, and resolution. As previously reported, peripheral neuropathy (PN; 67%), infections (60%), and neutropenia (35%) were the most common BV-associated treatment-emergent AEs. Neutropenia was managed with dose delays and granulocyte colony-stimulating factor; no dose reductions or discontinuations were required. Most PN cases (57%) were managed with dose delays and reductions. The median time to PN onset was 13.7 weeks (range, .1 to 47.4). After the end of treatment, PN continued to resolve; symptom resolution was similar to that in the placebo arm at 3 years, demonstrating reversibility. BV had no significant impact on pre-existing PN. Patients with PN-related dose modifications had progression-free survival (PFS) comparable with patients without. Other less common but serious AEs, including pulmonary toxicities, hepatotoxicity, and cardiotoxicity, were rare in both arms and were managed with BV dose modifications or discontinuations. Secondary malignancies were rare and reported in patients with comorbidities or other risk factors. Consolidation therapy with BV for patients with HL at high risk of relapse after auto-HSCT is associated with sustained PFS. The most common AEs in the BV arm were manageable and reversible. Awareness of these AEs and management approaches will enable healthcare providers and patients to plan the safest and most effective treatment plan.

Calcineurin and mTOR Inhibitor-Free Post-Transplantation Cyclophosphamide and Bortezomib Combination for Graft-versus-Host Disease Prevention after Peripheral Blood Allogeneic Hematopoietic Stem Cell Transplantation: A Phase I/II Study.

Graft-versus-host disease (GVHD) hampers the utility of allogeneic hematopoietic stem cell transplantation (AHSCT). The purpose of this study was to determine the feasibility, safety, and efficacy of a novel combination of post-transplantation cyclophosphamide (PTC) and bortezomib for the prevention of GVHD. Patients undergoing peripheral blood AHSCT for hematological malignancies after reduced-intensity conditioning with grafts from HLA-matched related or unrelated donors were enrolled in a phase I/II clinical trial. Patients received a fixed dose of PTC and an increasing dose of bortezomib in 3 cohorts, from .7 to 1 and then to 1.3 mg/m2, administered 6 hours after graft infusion and 72 hours thereafter, during phase I. The study was then extended at the higher dose in phase II for a total of 28 patients. No graft failure and no unexpected grade ≥3 nonhematologic toxicities were encountered. The median times to neutrophil and platelet engraftment were 16 and 27 days, respectively. Day +100 treatment-related mortality was 3.6% (95% confidence interval [CI], .2% to 15.7%). The cumulative incidences of grades II to IV and grades III and IV acute GVHD were 35.9% (95% CI, 18.6% to 53.6%) and 11.7% (95% CI, 2.8% to 27.5%), respectively. The incidence of chronic GVHD was 27% (95% CI, 11.4% to 45.3%). Progression-free survival, overall survival, and GVHD and relapse-free survival rates were 50% (95% CI, 30.6% to 66.6%), 50.8% (95% CI, 30.1% to 68.2%), and 37.7% (95% CI, 20.1% to 55.3%), respectively. Immune reconstitution, measured by CD3, CD4, and CD8 recovery, was prompt. The combination of PTC and bortezomib for the prevention of GVHD is feasible, safe, and yields promising results. The combination warrants further examination in a multi-institutional trial.

Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial.

BACKGROUND: Lenalidomide plus dexamethasone is a reference treatment for patients with newly diagnosed myeloma. The combination of the proteasome inhibitor bortezomib with lenalidomide and dexamethasone has shown significant efficacy in the setting of newly diagnosed myeloma. We aimed to study whether the addition of bortezomib to lenalidomide and dexamethasone would improve progression-free survival and provide better response rates in patients with previously untreated multiple myeloma who were not planned for immediate autologous stem-cell transplant. METHODS: In this randomised, open-label, phase 3 trial, we recruited patients with newly diagnosed multiple myeloma aged 18 years and older from participating Southwest Oncology Group (SWOG) and National Clinical Trial Network (NCTN) institutions (both inpatient and outpatient settings). Key inclusion criteria were presence of CRAB (C=calcium elevation; R=renal impairment; A=anaemia; B=bone involvement) criteria with measurable disease (measured by assessment of free light chains), Eastern Cooperative Oncology Group (ECOG) performance status of 0-3, haemoglobin concentration 9 g/dL or higher, absolute neutrophil count 1 × 103 cells per mm3 or higher, and a platelet count of 80 000/mm3 or higher. We randomly assigned (1:1) patients to receive either an initial treatment of bortezomib with lenalidomide and dexamethasone (VRd group) or lenalidomide and dexamethasone alone (Rd group). Randomisation was stratified based on International Staging System stage (I, II, or III) and intent to transplant (yes vs no). The VRd regimen was given as eight 21-day cycles. Bortezomib was given at 1·3 mg/m2 intravenously on days 1, 4, 8, and 11, combined with oral lenalidomide 25 mg daily on days 1-14 plus oral dexamethasone 20 mg daily on days 1, 2, 4, 5, 8, 9, 11, and 12. The Rd regimen was given as six 28-day cycles. The standard Rd regimen consisted of 25 mg oral lenalidomide once a day for days 1-21 plus 40 mg oral dexamethasone once a day on days 1, 8, 15, and 22. The primary endpoint was progression-free survival using a prespecified one-sided stratified log rank test at a significance level of 0·02. Analyses were intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00644228. FINDINGS: Between April, 2008, and February, 2012, we randomly assigned 525 patients at 139 participating institutions (264 to VRd and 261 to Rd). In the randomly assigned patients, 21 patients in the VRd group and 31 in the Rd group were deemed ineligible based mainly on missing, insufficient, or early or late baseline laboratory data. Median progression-free survival was significantly improved in the VRd group (43 months vs 30 months in the Rd group; stratified hazard ratio [HR] 0·712, 96% CI 0·56-0·906; one-sided p value 0·0018). The median overall survival was also significantly improved in the VRd group (75 months vs 64 months in the Rd group, HR 0·709, 95% CI 0·524-0·959; two-sided p value 0·025). The rates of overall response (partial response or better) were 82% (176/216) in the VRd group and 72% (153/214) in the Rd group, and 16% (34/216) and 8% (18/214) of patients who were assessable for response in these respective groups had a complete response or better. Adverse events of grade 3 or higher were reported in 198 (82%) of 241 patients in the VRd group and 169 (75%) of 226 patients in the Rd group; 55 (23%) and 22 (10%) patients discontinued induction treatment because of adverse events, respectively. There were no treatment-related deaths in the Rd group, and two in the VRd group. INTERPRETATION: In patients with newly diagnosed myeloma, the addition of bortezomib to lenalidomide and dexamethasone resulted in significantly improved progression-free and overall survival and had an acceptable risk-benefit profile. FUNDING: NIH, NCI, NCTN, Millennium Pharmaceuticals, Takeda Oncology Company, and Celgene Corporation.

Cancer and treatment distress psychometric evaluation over time: A BMT CTN 0902 secondary analysis.

BACKGROUND: Routine monitoring of cancer-related distress is recognized as essential to quality care and mandated by a major accrediting organization. However, to the authors' knowledge, few cancer-specific measures have been developed to date to assess the multiple cancer-related factors contributing to this distress. In the current study, the authors examined the psychometric properties of the Cancer and Treatment Distress (CTXD) measure over time in hematopoietic cell transplantation (HCT) recipients. METHODS: As a secondary analysis of a multicenter randomized controlled clinical trial, adult patients undergoing autologous or allogeneic HCT completed patient-reported outcomes including the CTXD and the Medical Outcomes Study Short Form-36 (SF-36) before transplantation and 100 days and 180 days after HCT. RESULTS: Across 21 transplantation centers, a total of 701 patients consented, underwent transplantation, and were included in the current analyses, 645 of whom were alive at 100 days and 618 of whom were alive at 180 days. Internal consistency reliability was found to be strong for the overall CTXD at the 3 time points: Cronbach alphas (α) were .94, .95, and .95, respectively. Subscale reliability met hypothesized levels of an α>.70 across time, with the lowest reliability noted for the Identity subscale at 180 days (α = .77). Correlations with the SF-36 Mental Health subscale were higher than with the Physical Functioning subscale at each time point, thereby supporting convergent and discriminant validity. Strong correlations of the pretransplantation CTXD with the posttransplantation CTXD and SF-36 Mental Health subscale supported predictive validity. CONCLUSIONS: The CTXD is reliable and valid as a measure of cancer distress both before and after HCT. It may be a useful tool for measuring dimensions of distress and for defining those patients requiring treatment for distress during and after transplantation. Cancer 2017;123:1416-1423. © 2016 American Cancer Society.

Maintenance versus Induction Therapy Choice on Outcomes after Autologous Transplantation for Multiple Myeloma.

Bortezomib (V), lenalidomide (R), cyclophosphamide (C), and dexamethasone (D) are components of the most commonly used modern doublet (RD, VD) or triplet (VRD, CVD) initial induction regimens before autologous hematopoietic cell transplantation (AHCT) for multiple myeloma (MM) in the United States. In this study we evaluated 693 patients receiving "upfront" AHCT after initial induction therapy with modern doublet or triplet regimens using data reported to the Center for International Blood and Marrow Transplant Research from 2008 to 2013. Analysis was limited to those receiving a single AHCT after 1 line of induction therapy within 12 months from treatment initiation for MM. In multivariate analysis, progression-free survival (PFS) and overall survival were similar irrespective of induction regimen. However, high-risk cytogenetics and nonreceipt of post-transplant maintenance/consolidation therapy were associated with higher risk of relapse. Patients receiving post-transplant therapy had significantly improved 3-year PFS versus no post-transplant therapy (55% versus 39%, P = .0001). This benefit was most evident in patients not achieving at least a complete response post-AHCT (P = .005). In patients receiving upfront AHCT, the choice of induction regimen (doublet or triplet therapies) appears to be of lower impact than use of post-transplant therapy.

Quality of life results from a phase 3 study of brentuximab vedotin consolidation following autologous haematopoietic stem cell transplant for persons with Hodgkin lymphoma.

Brentuximab vedotin (BV) significantly improved progression-free survival in a phase 3 study in patients with relapsed or refractory Hodgkin lymphoma (RR-HL) post-autologous-haematopoietic stem cell transplant (auto-HSCT); we report the impact of BV on quality of life (QOL) from this trial. The European Quality of Life five dimensions questionnaire was administered at the beginning of each cycle, end of treatment, and every 3 months during follow-up; index value scores were calculated using the time trade-off (TTO) method for UK-weighted value sets. Questionnaire adherence during the trial was 87·5% (N = 329). In an intent-to-treat analysis, compared with placebo, TTO scores in the BV arm did not exceed the minimally important difference (MID) of 0·08 except at month 15 (-0·084; 95% confidence interval, -0·143 to -0·025). On-treatment index scores were similar between arms and did not reach the MID at any time point; mixed-effect modelling showed that BV treatment effect was not significant (P = 0·2127). BV-associated peripheral neuropathy did not meaningfully impact QOL. Utility scores for patients who progressed declined compared with those who did not; TTO scores between these patients exceeded the MID beginning at month 15. In conclusion, QOL decreased modestly with BV consolidation treatment in patients with RR-HL at high risk of relapse after auto-HSCT.

Post-Transplant Outcomes in High-Risk Compared with Non-High-Risk Multiple Myeloma: A CIBMTR Analysis.

Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (<45 chromosomes excluding -Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher compared with non-HRM (56% versus 43%, P < .001) with similar pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100 post-transplant, at least a very good partial response was 59% in HRM and 61% in non-HRM (P = .6). More HRM patients received post-transplant therapy with bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were 37% versus 49% (P < .001) and 72% versus 85% (P < .001), respectively. At 3 years, PFS for HRM patients with and without post-transplant therapy was 46% (95% confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus 39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post-transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65) compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM patients with and without post-transplant therapy, respectively. Among patients receiving post-transplant therapy, there was no difference in OS between HRM and non-HRM (P = .08). In addition to HRM, higher stage, less than a CR pretransplant, lack of post-transplant therapy, and African American race were associated with worse OS. In conclusion, we show HRM patients achieve similar day 100 post-transplant responses compared with non-HRM patients, but these responses are not sustained. Post-transplant therapy appeared to improve the poor outcomes of HRM.

Patient-Reported Outcomes and Socioeconomic Status as Predictors of Clinical Outcomes after Hematopoietic Stem Cell Transplantation: A Study from the Blood and Marrow Transplant Clinical Trials Network 0902 Trial.

This secondary analysis of a large, multicenter Blood and Marrow Transplant Clinical Trials Network randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes, including time to hematopoietic recovery, acute graft-versus-host disease, hospitalization days, and overall survival (OS) among 646 allogeneic and autologous HCT recipients. Pretransplantation Cancer and Treatment Distress (CTXD), Pittsburgh Sleep Quality Index (PSQI), and mental and physical component scores of the Short-Form 36 were correlated with each other and with SES variables. PROs and SES variables were further evaluated as predictors of clinical outcomes, with the PSQI and CTXD evaluated as OS predictors (P < .01 considered significant given multiple testing). Lower attained education was associated with increased distress (P = .002), lower income was related to worse physical functioning (P = .005) and increased distress (P = .008), lack of employment before transplantation was associated with worse physical functioning (P < .01), and unmarried status was associated with worse sleep (P = .003). In this large heterogeneous cohort of HCT recipients, although PROs and SES variables were correlated at baseline, they were not associated with any clinical outcomes. Future research should focus on HCT recipients at greater psychosocial disadvantage.

Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity.

This phase Ib clinical trial evaluated whether pretargeting of CD20(+) clonogenic myeloma precursor cells (CMPCs) with anti-CD3 × anti-CD20 bispecific antibody-armed T cells (BATs) before autologous stem cell transplantation (SCT) in patients with standard-risk and high-risk multiple myeloma would induce antimyeloma immunity that could be detected and boosted after SCT. All 12 patients enrolled in this study received 2 BATs infusions before SCT, and 4 patients received a booster infusion of BATs after SCT. Pretargeting CD138(-)/CD20(+) CMPCs with BATs before SCT was safe and reduced levels of CMPCs by up to 58% in the postinfusion bone marrow in patients who remained in remission. Four of 5 patients who remained in remission had a >5-fold increase in IFN-γ enzyme-linked immunospot responses. SOX2 antibody increased after BATs infusions and persisted after SCT. The median anti-SOX2 level at 3 months after SCT was 28.1 ng/mL (range, 4.6 to 256 ng/mL) in patients who relapsed and 46 ng/mL (range, 28.3 to 73.3 ng/mL) in patients who remained in remission. The immune correlates suggest that infusions of targeted T cells given before SCT were able to reduce CMPC levels and induced cellular and humoral antimyeloma immunity that could be transferred and boosted after SCT.

Patient-reported physical functioning predicts the success of hematopoietic cell transplantation (BMT CTN 0902).

BACKGROUND: In hematopoietic cell transplantation (HCT), current risk adjustment strategies are based on clinical and disease-related variables. Although patient-reported outcomes (PROs) predict mortality in multiple cancers, they have been less well studied within HCT. Improvements in risk adjustment strategies in HCT would inform patient selection, patient counseling, and quality reporting. The objective of the current study was to determine whether pre-HCT PROs, in particular physical health, predict survival among patients undergoing autologous or allogeneic transplantation. METHODS: In this secondary analysis, the authors studied pre-HCT PROs that were reported by 336 allogeneic and 310 autologous HCT recipients enrolled in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902 protocol, a study with broad representation of patients who underwent transplantation in the United States. RESULTS: Among allogeneic HCT recipients, the pre-HCT Medical Outcomes Study Short Form-36 Health Survey (SF-36) physical component summary (PCS) scale independently predicted overall mortality (hazards ratio, 1.40 per 10-point decrease; P<.001) and performed at least as well as currently used, non-PRO risk indices. Survival probability estimates at 1 year for the first, second, third, and fourth quartiles of the baseline PCS were 50%, 65%, 75%, and 83%, respectively. Early post-HCT decreases in PCS were associated with higher overall and treatment-related mortality. When adjusted for patient variables included in the US Stem Cell Therapeutic Outcomes Database model for transplant center-specific reporting, the SF-36 PCS retained independent prognostic value. CONCLUSIONS: PROs have the potential to improve prognostication in HCT. The authors recommend the routine collection of PROs before HCT, and consideration of the incorporation of PROs into risk adjustment for quality reporting.

Significant Improvements in the Practice Patterns of Adult Related Donor Care in US Transplantation Centers.

Recent investigations have found a higher incidence of adverse events associated with hematopoietic cell donation in related donors (RDs) who have morbidities that if present in an unrelated donor (UD) would preclude donation. In the UD setting, regulatory standards ensure independent assessment of donors, one of several crucial measures to safeguard donor health and safety. A survey conducted by the Center for International Blood and Marrow Transplant Research (CIBMTR) Donor Health and Safety Working Committee in 2007 reported a potential conflict of interest in >70% of US centers, where physicians had simultaneous responsibility for RDs and their recipients. Consequently, several international organizations have endeavored to improve practice through regulations and consensus recommendations. We hypothesized that the changes in the 2012 Foundation for the Accreditation of Cellular Therapy and the Joint Accreditation Committee-International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation standards resulting from the CIBMTR study would have significantly impacted practice. Accordingly, we conducted a follow-up survey of US transplantation centers to assess practice changes since 2007, and to investigate additional areas where RD care was predicted to differ from UD care. A total of 73 centers (53%), performing 79% of RD transplantations in the United States, responded. Significant improvements were observed since the earlier survey; 62% centers now ensure separation of RD and recipient care (P < .0001). This study identifies several areas where RD management does not meet international donor care standards, however. Particular concerns include counseling and assessment of donors before HLA typing, with 61% centers first disclosing donor HLA results to an individual other than the donor, the use of unlicensed mobilization agents, and the absence of long-term donor follow-up. Recommendations for improvement are made.

BEAM Conditioning Regimen Has Higher Toxicity Compared With High-Dose Melphalan for Salvage Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

BACKGROUND: Salvage autologous stem cell transplantation (ASCT) is increasingly used for eligible patients with multiple myeloma (MM) for progress after conventional chemotherapy. We recently used BEAM (BCNU, etoposide, cytarabine, and melphalan) conditioning for patients with myeloma receiving salvage ASCT whose disease progressed after a first ASCT with high-dose melphalan (HDM). We report safety and efficacy of BEAM salvage ASCT in MM in comparison with HDM-based salvage ASCT. PATIENTS AND METHODS: Between 2008 and 2013, 43 consecutive patients received salvage ASCT for MM (19 with HDM; 24 with BEAM). RESULTS: The BEAM group had a higher incidence of infections, intensive level of care, and fever (19 vs. 13 patients; P = .02), whereas the melphalan group had a higher incidence of mucositis (7 vs. 2 patients; P = .03). Other toxicities were not different. There was no significant difference in disease status and response rate before and after salvage ASCT between the 2 groups. The median time of follow-up after salvage ASCT was 5 and 9 months and the median progression-free survival (PFS) times were 7.7 and 12.1 months (P = .82) for BEAM and melphalan, respectively. CONCLUSION: BEAM seemed to be associated with higher toxicity with comparable efficacy to HDM ASCT. Longer follow-up is needed to determine whether there is any significant difference in PFS between the 2 groups.

Analysis of the Effect of Race, Socioeconomic Status, and Center Size on Unrelated National Marrow Donor Program Donor Outcomes: Donor Toxicities Are More Common at Low-Volume Bone Marrow Collection Centers.

Previous studies have shown that risks of collection-related pain and symptoms are associated with sex, body mass index, and age in unrelated donors undergoing collection at National Marrow Donor Program centers. We hypothesized that other important factors (race, socioeconomic status [SES], and number of procedures at the collection center) might affect symptoms in donors. We assessed outcomes in 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors collected between 2004 and 2009. Pain/symptoms are reported as maximum levels over mobilization and collection (PBSC) or within 2 days of collection (BM) and at 1 week after collection. For PBSC donors, race and center volumes were not associated with differences in pain/symptoms at any time. PBSC donors with high SES levels reported higher maximum symptom levels 1 week after donation (P = .017). For BM donors, black males reported significantly higher levels of pain (OR, 1.90; CI, 1.14 to 3.19; P = .015). No differences were noted by SES group. BM donors from low-volume centers reported more toxicity (OR, 2.09; CI, 1.26 to 3.46; P = .006). In conclusion, race and SES have a minimal effect on donation-associated symptoms. However, donors from centers performing ≤ 1 BM collection every 2 months have more symptoms after BM donation. Approaches should be developed by registries and low-volume centers to address this issue.