Gastineau, Dennis A.

Objectives: Modifiable lifestyle factors are associated with morbidity and mortality in hematopoietic stem cell transplant (HSCT) survivors. The aims of the study were to examine: (a) receipt of provider advice to change behaviors, (b) health behavior change, and (c) how modifiable lifestyle factors might cluster together. Methods: Patients within a large HSCT program completed a survey (N =870) of lifestyle factors at pre-HSCT evaluation. The survey assessed self-reported adherence to American Cancer Society and HSCT guidelines for cancer survivorship in the year prior to a pre-HSCT evaluation. Lifestyle factors of interest were physical activity, fruit and vegetable consumption, tobacco use, alcohol use, and height/weight to calculate Body Mass Index (BMI). Results: Among patients not meeting all five guidelines (98%), 31% received provider advice to change. Between 10% and 42% reported healthy behavior change since diagnosis. Physical activity, fruit and vegetable consumption, and BMI were the most commonly clustered lifestyle behaviors. Conclusions: A considerable proportion of patients did not meet national guidelines for lifestyle factors. Results highlight an immediate opportunity to improve health care delivery and transplant outcomes via pre-HSCT lifestyle screening and implementation of effective health behavior change interventions.

ABSTRACTObjectiveTo explore pre–hematopoietic stem cell transplant (HSCT) demographic, disease, and psychological factors predictive of future transplant regret and to determine post‐HSCT variables associated with regret.Patients and MethodsHSCT candidates participated in a prospective cohort study (June 2008–October 2013) examining health behaviors and HSCT outcomes, including completion of standardized surveys at pre‐HSCT (baseline) and 1‐year post‐HSCT. Cases were participants that endorsed regret at 1‐year post‐HSCT follow‐up, and controls were participants without regret at 1 year, matched on age, sex, and transplant type. For cases and controls, pre‐HSCT psychosocial evaluations were abstracted from the electronic health record and coded to determine the Psychosocial Assessment of Candidates for Transplantation score, psychosocial stressors, and mental health diagnoses. The association of selected factors with regret was estimated with odds ratios and 95% confidence intervals from conditional logistic regression models.ResultsAt post‐HSCT, 49 participants of 638 endorsed transplant regret (8%) and formed the case group; 98 controls were matched from remaining participants. Cases and controls were well matched on age (56.6 vs. 57.2 years), sex (both groups 34.7% female), and transplant type (both groups 81.6% autologous). After controlling for the number of hospitalizations and active treatment status, conditional logistic regression revealed that patients who endorsed regret were 3.7 times (95% CI = 1.37–9.69, p = 0.008) more likely to not be in remission compared to controls at 1‐year post‐HSCT.ConclusionMatched case–control analyses revealed that no pre‐HSCT variables collected during the pre‐HSCT evaluation period were predictive of transplant regret, while poorer outcomes at 1‐year after transplant were associated with regret.

AbstractPurpose: Absolute lymphocyte count recovery at day 15 (ALC-15) post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival for multiple hematologic malignancies and metastatic breast cancer. The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown.Experimental Design: We evaluated 145 consecutive patients with primary systemic amyloidosis who underwent ASCT at the Mayo Clinic from 1996 to 2003. The ALC-15 threshold was set at 500 cells/μL based on our previous observations.Results: The median patient follow-up was 22 months (range, 3-87 months). Higher hematologic complete response was observed in patients with an ALC-15 ≥ 500 cells/μL compared with patients with an ALC-15 < 500 cells/μL (41% versus 21%, P < 0.0008, respectively). The median overall survival and progression-free survival times were significantly better for the 59 patients that achieved an ALC-15 ≥ 500 cells/μL compared with 86 patients with ALC-15 < 500 cells/μL (not reached versus 53 months, P < 0.0003 and not reached versus 27 months, P < 0.0001, respectively). Multivariate analysis showed ALC-15 to be an independent prognostic factor for overall survival and progression-free survival.Conclusions: ALC-15 ≥ 500 cells/μL is associated with significantly improved clinical outcomes following ASCT in patients with primary systemic amyloidosis.

The remarkable success of cancer immunotherapies has provided new hope to cancer patients. Unfortunately, a significant proportion of patients remain unable to respond to immunotherapy or maintain durable clinical responses. The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients. As the immune system is highly responsive to exercise, one potential avenue to improve immune function is through exercise and physical activity. A single event of dynamic exercise results in the substantial mobilization of leukocytes with increased functional capacities into the circulation. Chronic, or long-term, exercise leads to higher physical fitness in terms of greater cardiorespiratory function and/or muscle strength and endurance. High aerobic capacity, as measured by maximal oxygen uptake, has been associated with the reduction of dysfunctional T cells and improvements in the abundance of some T cell populations. To be sure, however, the mechanisms of exercise-mediated immune changes are both extensive and diverse. Here, we examine the evidence and theorize how acute and chronic exercise could be used to improve responses to cancer immunotherapies including immune checkpoint inhibitors, dendritic cell vaccines, natural killer cell therapies, and adoptive T cell therapies such as chimeric antigen receptor (CAR) T cells. Although the parameters of optimal exercise to yield defined outcomes remain to be determined, the available current data provide a compelling justification for additional human studies and clinical trials investigating the adjuvant use of exercise in immuno-oncology.

7039 Background: Erythropoiesis-stimulating agents are known to increase the risk for VTE events, especially in patients with underlying malignancies. However, there is a paucity of information on other hematopoietic growth factors such as granulocyte colony-stimulating factor (GSCF) granulocyte-macrophage colony stimulating factor (GM-CSF) AMD 3001 and risk for VTE. Methods: Between January 2000 and October 2008, a total of 631 patients underwent peripheral blood stem cell mobilization (PBSCM) using either GCSF, GMCSF, cyclophosphamide, AMD 3100, or with any of the above combination. We included only patients with a diagnosis of AL amyloidosis (AL), multiple myeloma (MM) Hodgkin's lymphoma (HL) and non Hodgkin's lymphoma (NHL). Patients’ demographic details and diagnosis of VTE were collected from electronic medical records. Results: Of the 631 patients who underwent PBSCM the median age of the patients was 57 years (range 17–77). 448 patients (71%) received single agent GCSF, 82 (13%) received combination of GMCSF and cyclophosphamide, 52 (8%) received cyclophosphamide and GCSF, 30 patients received a combination of GMCSF and GCSF, 10 (1.5%) patients received GCSF and AMD 3100. Of the 631 patients, 278 (44%) MM, 209 (33%) NHL, 114 (18%) AL, and 20 (3%) had HL. We found 7 (1.1%) patients with symptomatic VTE occurring between administration of growth factors and stem cell transplant. The median duration from the administration of growth factors to detection of VTE was 5 days (range 1–30). Two AL,3 MM and 2 NHL. Of the 7 patients, 2 patients had pulmonary embolism and 1 patient developed deep vein thrombosis. Two patients with AL developed heparin induced thrombocytopenia (HIT). The remaining 4 patients developed symptomatic catheter related thrombosis. Only 1 patient had past history of VTE. Of the 7 patients, 5 received GCSF alone, 1 received GMCSF, and cyclophosphamide, 1 received GCSF and cyclophosphamide. Of the 4 patients who developed catheter related thrombosis, catheter was removed in 2 patients. None of the patients developed VTE related morality. Conclusions: The risk for symptomatic VTE during PBSCM is low. HIT should be considered as a possible cause for VTE in patients undergoing PBSCM. No significant financial relationships to disclose.

Abstract Introduction: The association of amyloidosis with immunoglobulin light chain disorders is well recognized. It is less commonly appreciated that amyloidosis can be associated with IgM monoclonal gammopathies. One of the available therapies for treating amyloidosis is stem cell transplantation. It is unknown whether the clinical outcomes in patients with IgM amyloidosis differs from those patients with light chain amyloidosis. Patients: Among 242 amyloidosis patients receiving stem cell transplants 10 (4%) had an IgM monoclonal protein. Eight were Mλ. One was biclonal Mλ Mκ and one was biclonal Mκ Gλ. The age range was 56 to 71, median 64 years. Seven were men. The monoclonal protein ranged in size from 0.1 to 2.3 g/dL (median 1.2 g/dL). Patients were transplanted from 2 to 8 months (median 4 months) following histologic diagnosis of amyloid. The median time from the recognition of the IgM monoclonal protein to the diagnosis of amyloid was 1.3 months, but 2 patients, both of whom had overt Waldenström’s macroglobulinemia, were diagnosed 45 and 115 months respectively before amyloidosis developed. Of the cohort of 10, 3 fulfilled the criteria for symptomatic Waldenström’s macroglobulinemia. Results: Amyloid syndromes were recognized in the kidney, heart, peripheral nerve and liver in 8, 3, 3 and 1 patient, respectively. Of the 3 peripheral neuropathy patients one also had autonomic failure. Seven of the 8 renal amyloid patients were confirmed with a renal biopsy. Their urinary protein loss ranged from 0.1 to 9.5 g/24h with a median of 4.7 g/24h. Six of the 10 patients had single organ involvement, 3 had 2 organ involvement and 1 had 3 organ involvement. All 3 Waldenström’s patients had prior exposure to cytotoxic chemotherapy. Amyloid deposits were seen in the bone marrow, fat and lymph node in 6, 5 and 1 patient, respectively. Patients underwent from 1 to 7 (median 3) apheresis with a median CD34 yield of 4.5 x 106/kg. Conditioning was Melphalan at 140 and 200 mg/m2 in 2 and 8 patients respectively. Neutrophil engraftment 500/μL occurred between day 11 and 30 (median 14) and for platelets 20,000/μL between day 11 and 406 (median day 16). The median number of hospitalization days ranged from 0 to 32 (median 12). Nine of the 10 patients fulfilled criteria for a hematologic response and to date 3 of these 9 have also achieved an organ response, including normalization of urinary protein loss in 2 nephrotic patients and a greater than 50% reduction in urinary protein loss in the third. None of the patients with amyloid neuropathy responded. One of the patients with cardiac amyloid showed echocardiographic evidence of improvement. At this time 8 survive and 2 died; 1 a treatment-related death (day +40) and 1 of relapse post transplant with progressive amyloid at 45 months. The median follow-up of surviving patients is 29 months. Conclusion: The outcomes in patients with IgM amyloidosis following transplantation do not appear to be different from those with immunoglobulin light chain amyloidosis. There is no suggestion that the response rates are lower or that alternate conditioning schemes such as BEAM should be considered.

Abstract INTRODUCTION Stem cell transplant has been increasingly used in the initial therapy of newly diagnosed systemic AL. Introduction of the free light chain assay has made it easier to quantify responses in patients with AL. It is unclear whether the goal of therapy should be a hematologic response or, as in multiple myeloma, a complete response. This paper addresses the impact of the degree of response on outcome. PATIENTS AND METHODS 282 consecutively transplanted patients are included in this analysis. None of the patients were excluded. There were 169 men (59%). 28% of the cohort have died. 69% had renal involvement, 51% cardiac involvement, 11% peripheral nerve involvement, 16% hepatic involvement. The median percentage of plasma cells at the time of transplant was 7. Echocardiographic analysis revealed a median septal thickness of 12 and a median ejection fraction of 65%. Patients ranged in age from 31 to 71 with a median of 57 years and were transplanted at a median of 4.2 months following histologic diagnosis of amyloidosis. 27% of patients received reduced intensity conditioning usually due to moderate cardiomyopathy or renal insufficiency. 201 patients achieved a hematologic response and 93 of these achieved a complete response. The criteria for response were reported in accord with the consensus definition for response established at The Xth International Symposium on Amyloid and Amyloidosis. A complete response required immunofixation negativity of serum and urine with a normal free light chain ratio. A hematologic objective response required a 50% reduction of serum and urine monoclonal protein with a 50% reduction in the free light chain value. Figure 1 shows the Kaplan Meier curves demonstrating the survival of all patients based on whether they achieved a complete response, partial response, or failed to achieve response. There were 93 CR, 108 PR, and 81 nonresponders. The differences in all three curves are significant at P<.001. Figure 2 demonstrates the same cohort of patients using a six month landmark analysis to exclude the effect of treatment related mortality on outcome. There were 86 CR, 91 PR, and 36 NR for a total of 213 patients. There was a difference in response rate based on conditioning intensity (p<0.01) and age (p=0.046). The median survival was only reached in the NR at 40.1 months and, in the landmark analysis the differences between all three survival curves were statistically significant. CONCLUSION Patients who achieve a hematologic complete response following sct for AL do better than other patients. Patients who achieve an objective response have a superior outcome than patients who fail to achieve a hematologic response, in a landmark analysis at six months. It is unclear if consolidation chemotherapy should be offered to partial responders in an attempt to convert them into CR’s. Figure Figure Figure Figure

Abstract AMD3100, a CXCR4 receptor antagonist, has been studied as a stem cell mobilization agent for the purpose of autologous stem cell transplantation (ASCT) in hematologic malignancies. Lymphocyte subset analysis of peripheral blood in patients treated with AMD3100 has been studied in healthy volunteers. To date, no reports exist describing the lymphocyte subsets of the autograft in patients undergoing AMD3100 stem cell mobilization for the purposes of ASCT in non-Hodgkin lymphoma (NHL). Considering our prior work demonstrating the significant impact of autograft lymphocyte content on clinical outcomes of patients undergoing ASCT for NHL we set out to profile autograft lymphocyte subsets of patients undergoing mobilization with AMD3100. Using flow cytometry, we analyzed aliquots of apheresis products in 7 patients with NHL undergoing AHSCT who received AMD3100 in addition to G-CSF as a part of their mobilization regimen. These results were compared to 29 patients with NHL who had undergone stem cell mobilization with G-CSF alone. There were no significant differences between these two groups of patients in terms of sex, age, performance status, histology, LDH, and number of pretransplant chemotherapeutic regimens. CD34+ cells collected at apheresis did not differ significantly between the groups. However, compared with G-CSF alone, patients that received AMD3100 had an approximate 5-fold increase in CD4+ cells (0.62 x 109 cells/kg vs. 0.12 x 109 cells/kg, p = 0.0004), a 3.5-fold increase in the absolute number of autograft CD3+ cells (1.21 x 109 cells/kg vs. 0.33 x 109 cells/kg, p = 0.0017), and a 2.5-fold increase in CD8+ cells (0.48 x 109 cells/kg vs 0.19 x 109 cells/kg, p = 0.215). A significant increase was also noted in CD4+25+ cell compartment (0.17 x 109 cells/kg vs. 0.006 x 109 cells/kg, p = 0.0001). No significant difference was noted in the absolute number of autograft CD16+56+ NK cells. Finally, an increase in the autograft total absolute lymphocyte count (41.6 x 109 cells/kg vs. 2.88 x 109 cells/kg, p < 0.001) as well as peripheral blood absolute lymphocyte count at day 15 after AHSCT was observed in those patients who had received AMD3100 (0.79 x 109 cells/kg vs. 0.58 x 109 cells/kg, p = 0.04). The increased lymphocyte content of the autograft (total and subset) would suggest the potential of positive impact on clinical outcomes in patients mobilized with AMD3100. Indeed, none of the patients who received AMD3100 had relapsed disease at one year post-transplant (although two of these patients are currently 9 months and 11 months post-transplant respectively), whereas 10 of the 29 control patients had relapsed disease at one year. Further studies are necessary to confirm these observations and ascertain their clinical significance.

Abstract Mantle-cell lymphoma (MCL) is characterized by an aggressive clinical course and poor prognosis with a median survival of only 3 to 4 years. High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is an effective treatment strategy for MCL demonstrating significantly prolongs progression free survival (PFS) when compared to IFNa maintenance therapy of patients in first remission. We have previously shown that absolute lymphocyte count at day 15 (ALC-15) after ASCT is an independent prognostic factor for survival in hematologic malignancies (non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease, multiple myeloma, primary amyloidosis, acute myelogenous leukemia) and breast cancer. The study of ALC-15 after ASCT as a prognosis factor in NHL included different subtypes of lymphomas. The relationship of ALC-15 after ASCT in patients with MCL has not been specifically addressed. Herein we present data evaluating the impact of early lymphocyte recovery (ALC-15) in patients undergoing ASCT for MCL. We retrospectively reviewed the medical records of 42 consecutive patients (9 females and 33 males) with MCL who underwent ASCT at the Mayo Clinic in Rochester from 1993 to 2005. Based on our previous studies, the ALC-15 threshold was set at 500 cells/μL. The median patient age at transplant was 57 years (range, 37–71) and the median follow-up after ASCT was 25 months (range, 2–106 months). The median overall (OS) and PFS times were significantly better for the 24 patients that achieved an ALC-15 ≥ 500 cells/mL compared with 18 patients with ALC-15 < 500 cells/μL (not reached versus 30 months, P < 0.01 and not reached versus 16 months, P < 0.0006, respectively). Multivariate analysis adjusting for other prognostic factors suggests that ALC-15 is an independent prognostic factor for OS and PFS. ALC-15 ≥ 500 cells/mL is associated with significantly improved clinical outcomes following ASCT in patients with MCL.