scholarly journals Late Effects of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation (HDT-AHCT) in Elderly Patients with Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4620-4620
Author(s):  
Parastoo B. Dahi ◽  
Chikaodi Obioha ◽  
Sheila Kenny ◽  
Patrick Hilden ◽  
Molly Maloy ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Median Time ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Disease Stage ◽  
High Dose ◽  
Long Term Effects ◽  
Post Transplant ◽  
Number Of Patients

Abstract Background: High-dose chemotherapy and autologous hematopoietic cell transplantation (HDT-AHCT) is an established treatment for non-Hodgkin lymphoma (NHL). Incidence of NHL is highest in patients over 60 years of age, however, limited data is available on long-term effects of HDT-AHCT in older patients. This study is conducted to evaluate the late cardiopulmonary effects and overall outcomes of HDT-AHCT in older patients. Methods: This is a single-center, retrospective study examining late cardiopulmonary effects, and overall outcomes of HDT-AHCT in 41 patients age 70 years and older, with NHL, between January 2000 and December 2016. Clinical data and comorbidities were correlated with outcomes. Pre- and post-transplant pulmonary function tests (PFT) and echocardiograms were compared. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age, gender, disease histology, disease stage at diagnosis, number of lines of treatment, Karnofsky Performance Status (KPS), hemoglobin adjusted diffusing capacity of lungs for carbon monoxide (DLCO), left ventricular ejection fraction (LVEF), and hematopoietic cell transplantation comorbidity index (HCT-CI) at the time of HDT-AHCT. Results: A total of 41 patients underwent HDT-AHCT for follicular or diffuse large B-cell lymphoma (FL / DLBCL n=18 44%), mantle cell lymphoma (MCL n=15 37%) and T-cell or other NHL subtypes (n=8 19%). The median age was 72 (range 70-77). Eight (19%), 6 (15%) and 27 (66%) patients had a low (0), intermediate (1-2) and high (≥3) HCT-CI score, respectively, at transplant. All patients except 1, had received anthracycline as part of initial treatment. BEAM and RR-BEAM were the most common conditioning regimens (n=38 93%). Pre-transplant LVEF was within normal range in all patients except 1 (45%). The median (range) pre- and post-transplant LVEF was 63% (45-74%) and 64% (39-71%), respectively. Of the 23 patients who had a post-transplant echocardiogram (median time between the pre- and post-transplant echocardiogram was 423 days), a mild decrease in LVEF was noted in 3. Only 1 patient had a significant decline of 19% in LVEF. Pulmonary artery pressure (PAP) was within normal range pre- and post-transplant in all. The median (range) of pre-transplant DLCO, FEV1 and FVC were 70% (48-125%), 97% (83-141%), and 98% (57-123%), respectively. Of the 10 patients who underwent post-transplant PFT (median time between the pre- and post-transplant PFT was 405 days), DLCO decline of >10% was the most common abnormality, and developed in 4 out of 10 patients. In 5 patients DLCO improvement of >10% was observed. A greater than 15% improvement in FEV1 and FVC was observed in 5 of 10 and 4 of 10 patients respectively. The median improvements in FVC, FEV1 and DLCO were 4%, 6% and 10%, respectively. With a median follow-up of 58 months (range 5-123) for survivors, PFS and OS at 3 years were 84% (95% CI, 67-92%) and 94% (95% CI, 80-99%), respectively. In a univariate analysis, age, gender, histology, disease stage, number of lines of treatment, DLCO, LVEF, and HCT-CI score did not affect OS or PFS. However, KPS ≥90 was associated with worse OS (p=0.008). The small sample size may have been a contributor to this unexpected finding. Relapse occurred in 11 patients (27%), 8 of whom died. Median time to relapse was 38 months (range 26-100). Secondary malignancies developed in 4 patients (8%) which included acute myeloid leukemia in 2, melanoma in 1, and esophageal cancer in 1, and led to death in 3. Conclusion: In this cohort of elderly patients with NHL who underwent HDT-AHCT, the late declines in cardiopulmonary function were minimal, and none resulted in mortality. Secondary malignancy was the only cause of non-relapse mortality. This can be explained by age being the biggest single risk factor for cancer development in general, in addition to the effects of HDT. We show that the most common cause of long-term mortality after HDT-AHCT continues to be lymphoma recurrence. Our data though limited by small number of patients and its retrospective nature, suggest that age alone is not predictive of post-transplant late effects and outcomes, and therefore should not be used to preclude HDT-AHCT in elderly. While prospective studies with larger number of patients are needed to evaluate long-term effects of HDT-AHCT on different organ functions in older adults, strategies to mitigate risk of relapse remain the most important area to improve outcomes. Disclosures Sauter: Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy.

scholarly journals HEMATOPOIETIC CELL TRANSPLANTATION FOR OLDER PATIENTS WITH MDS

2014 ◽  
Vol 6 (1) ◽  
pp. e2014056 ◽  
Author(s):  
Mazyar Shadman ◽  
Joachim Deeg
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Disease Stage ◽  
Graft Versus Host ◽  
Therapeutic Modalities ◽  
Transplant Patients ◽  
Conditioning Regimens

The incidence of myeloid malignancies, including myelodysplastic syndromes (MDS) increases with age. While several therapeutic modalities have been developed, for most of these patients the only treatment with curative potential is allogeneic hematopoietic cell transplantation (HCT). The development of reduced/low intensity transplant conditioning regimens allows to successfully transplant patients in their ‘60s and even ‘70s, although comorbidities may determine who does come to transplantation and who does not. Also, as many as half of the patients will develop graft versus host disease (GVHD), even with HLA matched  donors, requiring therapy for extended periods of time,  and GVHD and treatment  with glucocorticoids is likely to impact the quality  of life. Nevertheless, dependent upon disease stage at HCT, the presence of comorbidities and the regimen used, 30% to 50% of patients  60 years of age or older, may survive long-term cured of their disease. Future studies should focus on the incorporation of non-transplant modalities into the overall transplant approach, the prevention of GVHD, and the utilization of immunotherapy to reduce the incidence of relapse and GVHD and further improve overall transplant success.

scholarly journals Lower Use of DLI Post Relapse of Malignancy May Result in Shorter Post-Relapse Survival (PRS) in Patients Undergoing T Cell Replete Haploidentical Donor Transplantation (HIDT) Versus Matched Related (MRD) or Matched Unrelated Donor (MUD) Hematopoietic Cell Transplantation (HCT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1967-1967
Author(s):  
Melhem Solh ◽  
Xu Zhang ◽  
Stacey Brown ◽  
Lawrence E. Morris ◽  
H. Kent Holland ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Median Time ◽  
Hematopoietic Cell Transplantation ◽  
Risk Index ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Comorbidity Index ◽  
Time To Relapse

Abstract Relapse of hematologic malignancies remains a major cause of treatment failure and mortality among patients receiving allogeneic hematopoietic cell transplantation (HCT). Patients relapsing after a matched related or unrelated donor transplantation may benefit from donor lymphocyte infusion (DLI) as part of their post relapse therapy. DLI post-relapse has less frequently been utilized among recipients of HIDT presumably due to the potential for severe GVHD if high T-cell doss are administered without immunosuppression. However, reluctance to administer DLI may limit the possibility of remission following disease relapse in HIDT. We compared the frequency of use of DLI and survival outcomes for patients relapsing after HIDT using post-transplant cyclophosphamide to those relapsing after MRD or MUD HCT at our institution. 195 consecutive HCT recipients with relapse of hematologic malignancy occurring after HIDT (N=35), MUD (N=74) and MRD (N=81) between 1998 and 2014 were included in this analysis. The median age was 50 years (19-77 years) and median time to relapse was 159 days (25-2465 days) post HCT. Patients receiving HIDT had similar median time to relapse (5.1 vs 5.2 vs 5.2 months, p=0.638), Dana-Farber/CIBMTR disease risk index (DRI), comorbidity index (CMI) scores, longer times to neutrophil engraftment (17 vs 14 vs 14 days, p<0.001), and platelet engraftment (28 vs 19 vs 18 days, p<0.001) when compared to MUD and MRD recipients respectively. Post-relapse survival at 1 year was worse among HIDT recipients when compared to MRD (9% versus 41%, p=0.008) and MUD (9% vs 35%, p=0.025). DLI was used in 3 (8%) relapsed HIDT patients, 48 MRD patients (59%) and 28 (38%) MUD recipients. Among patients relapsing post MRD and MUD HCT, use of DLI was associated with a better post relapse survival (p=0.04). In a multivariate analysis, donor type (HIDT), time to relapse (<3 months versus > 3months post-transplant) and comorbidity index (CMI score >= 3) were all predictive of worse post relapse survival. This analysis shows that relapse post HIDT carries a worse prognosis than relapse post MRD and MUD. Efforts such as post-transplant maintenance and haploidentical DLI infusions should be investigated further in the HIDT setting. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting

Blood ◽  
2009 ◽  
Vol 113 (14) ◽  
pp. 3383-3391 ◽  
Author(s):  
Marcello Rotta ◽  
Barry E. Storer ◽  
Firoozeh Sahebi ◽  
Judith A. Shizuru ◽  
Benedetto Bruno ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Initiation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Long Term Outcome ◽  
Autologous Hematopoietic Cell Transplantation

AbstractAutologous hematopoietic cell transplantation (HCT) followed by nonmyeloablative allogeneic HCT (auto/alloHCT) provides cytoreduction and graft-versus-myeloma effects. We report on long-term outcomes of 102 patients with multiple myeloma who received auto/alloHCT with a median follow-up of 6.3 years. Treatment consisted of high-dose melphalan and autograft followed by 2-Gy total body irradiation, with or without fludarabine, and alloHCT from human leukocyte antigen-identical siblings. Postgrafting immunosuppressive agent was cyclosporine or tacrolimus and mycophenolate mofetil. Forty-two percent of patients developed grade 2 to 4 acute graft-versus-host disease (GVHD) and 74% extensive chronic GVHD. Five-year nonrelapse mortality after allografting was 18%, 95% related to GVHD or infections. Among 95 patients with detectable disease, 59 achieved complete remissions. Median time to progression was 5 years. Median overall survival (OS) was not reached. Median progression-free survival (PFS) was 3 years. Five-year OS and PFS were 64% and 36%, respectively. Seventy-three patients receiving autoHCT within 10 months from treatment initiation had 5-year OS of 69% and PFS of 37%. In multivariate analysis, β-2-microglobulin of more than 3.5 μg/mL at diagnosis and auto/alloHCT more than 10 months after treatment initiation correlated with shorter OS (P = .03 and P = .02) and PFS (P = .04 and P = .03), whereas Karnofsky scores less than 90% at allotransplantation correlated with shorter PFS only (P = .005). Long-term disease control and GVHD remain key issues.

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