Multiple prognostic models for patients with advanced Hodgkin's disease have been developed in an effort to identify high-risk individuals for ASCT and predict outcomes of high dose therapy and ...transplant. The utility of four of these models was examined in a cohort of patients transplanted in our program between 1993 and 2005. A total of 113 patients with relapsed or refractory Hodgkin's disease received ASCT. Forty-five patients received a conditioning regimen of busulfan, melphalan, and thiotepa (BuMelTT) whereas 68 patients received other standard conditioning regimens (SCR) including Cy/TBI/VP (23), CBV (39), and other (6). Median age is 34.5 years for BuMelTT and 34.0 years for SCR patients. Ninety-eight percent of patients receiving BuMelTT had at least two or more prior regimens compared with 86% SCR patients. Eighty-seven percent of BuMelTT and 93% of SCR patients had chemosensitive disease prior to transplant. Median followup is 113 weeks for BuMelTT patients versus 201 weeks for SCR patients. To date 37% of the BuMelTT and 56% of SCR patients have relapsed (p<0.05) with a median time to relapse of 30 and 36 weeks (p=NS) respectively. Statistically significant factors differentiating the BuMelTT and SCR groups included median followup post-ASCT, total percent relapse after transplant, death after transplant, relapse in prior radiation field, and stage at salvage therapy pre-ASCT. Median OS, EFS, and RFS have not yet been reached for BuMelTT patients compared with 439 (p=0.03), 67 (p=NS), and 74 (p=NS) weeks for the SCR patients. TRM was five percent in both groups at five years. We investigated the predictive value of four prognostic models on the entire group, BuMelTT and SCR cohorts. Models evaluated included Roswell Park (RPCI), Memorial Sloan-Kettering, German Hodgkin's Study Group, and Southwestern Oncology Group (SWOG). Each of these models has identified three negative prognostic indicators on the basis of multivariate analysis. Patients who had 0 or 1 factor were considered good risk and those that had 2 or 3 factors poor risk. Only the SWOG model (>2 prior regimens, relapse in previous radiation field, extranodal disease) was predictive for OS for the entire group (p<0.01) and for the BuMelTT (p=0.05) and SCR (p<0.01) cohorts. The SWOG model was also able to differentiate EFS between good and poor risk patients for the entire group (p=0.02) and SCR group (p=0.05) but not for the BuMelTT cohort. None of the models could differentiate between good and poor risk patients with regard to RFS. When good and poor risk were defined as 0 factors versus 1 to 3 factors, the RPCI model (chemotherapy-resistant disease, poor performance status, and 3 or more chemotherapy regimens prior to transplant) was predictive of OS (p=0.02) and EFS (p=0.02) but only for the BuMelTT cohort. These results suggest that BuMelTT may improve long-term outcomes in patients with advanced Hodgkin's disease. The prognostic models evaluated had limited utility in our patient cohort with only the SWOG model being predictive of outcome. Large multi-institutional studies are needed to improve prognostic models for transplantation in advanced Hodgkin's disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Patients with diffuse large B-cell lymphoma (DLBCL) who present with extra-nodal involvement or histologic transformation from low-grade disease have lower rates of survival after ...conventional-dose therapy. The impact of these features on outcomes after high-dose therapy with autologous transplantation was investigated.
Methods: We retrospectively reviewed the outcomes of 64 consecutive patients receiving autologous transplantation from 1995 to 2003 for the treatment of DLBCL. Variables considered were age, gender, histologic transformation, history of bone marrow involvement, history of central nervous system (CNS) involvement, time from diagnosis to transplant, number of pre-transplant regimens, chemosensitivity prior to transplant, conditioning regimen, year of transplant, and the use of peripheral blood or bone marrow stem cells. Survivals were estimated by the Kaplan-Meier method. The Cox proportional hazards regression model was used to test the significance of factors on survival. Univariate association between variables and survival were tested by the log-rank test. Correlation between variables was tested with Spearman's rank coefficient.
Results: The median age at transplant among 64 patients was 53.5 years (17–74). The median overall survival was 3.3 years. Among these patients, 12 had a history of CNS involvement, 10 had a history of bone marrow involvement, and 12 had transformed from low-grade lymphoma. A Cox regression model suggested age <50 (log-rank, p=0.093), <2 regimens prior to transplant (log-rank, p=0.052), and the lack of BEAM as conditioning regimen (log-rank, p=0.019) as multivariate factors for survival. However, the use of BEAM was highly associated with older age (R²= 0.42, p=0.001) and more prior chemotherapy regimens (R²=0.24, p=0.054). A history of extranodal involvement, including prior CNS involvement (p=0.842) or bone marrow involvement (p=0.518), was not associated with lower survival by univariate analysis. No significant association was found between survival and a history of transformation (p=0.484).
Conclusions: A history of CNS involvement, bone marrow involvement, or histologic transformation is not associated with lower rates of survival among patients undergoing autologous transplantation for diffuse large B-cell lymphoma at our institution. Patients who present with such histories remain candidates for autologous transplantation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Bacterial infections, including infections with Gram-negative organisms, frequently complicate the post-engraftment phase after myeloablative allogeneic hematopoietic stem cell ...transplantation. In this pilot study, we investigated the safety and tolerability of administering antibacterial prophylaxis from the time of engraftment (absolute neutrophil count of >1500/mm3 for 2 days) through day +100. Moxifloxacin was chosen for its broad spectrum of bacterial coverage and for its ability to target both bacterial topoisomerase IV and DNA gyrase, limiting the development of antimicrobial resistance.
Methods: Twenty-three patients with engraftment after allogeneic transplantation at OHSU received moxifloxacin 400 mg po daily upon discontinuation of any antibiotics used for the treatment of pre-enrollment bacterial infection. Rates of bacterial infection, bacteremia, and colonization were recorded. Comparisons were made with a cohort of 60 consecutive patients undergoing myeloablative transplantation at OHSU without similar antibacterial prophylaxis from 2001–2002.
Results: The median duration of moxifloxacin prophylaxis was 77 days (range 7–87). Five patients had dose interruptions due to nausea associated with graft-versus-host disease and two patients elected not to restart study medication. Only 3 patients had dose interruptions during empiric antibiotic therapy for possible bacterial infection. Overall, moxifloxacin was well tolerated in this patient population, with 5 episodes of grade 3/4 toxicity felt possibly related to study drug (2 orthostatic hypotension in one patient, 2 nausea, and 1 hypertension). Five patients had episodes of transaminitis which were unlikely to be due to study medication, and which responded to discontinuation of antifungal therapy (4) or to treatment of liver GVHD (1). No cardiac arrhythmias or tendonopathy were observed. Compared to historic controls, a marked decrease in post-engraftment phase bacterial infections was observed. The control cohort, 16 patients experienced 17 episodes of Gram-negative and 22 patients had 25 episodes of symptomatic Gram-positive infections during the post-engraftment phase without prophylaxis. In contrast with moxifloxacin prophylaxis, 2 patients experienced 3 Gram-negative infections (χ2, p=0.079), 1 patient had an anaerobic infection, and 7 patients had 9 symptomatic Gram-positive infections.
Conclusions: Prophylactic moxifloxacin dosed throughout the post-engraftment phase has been well tolerated, safe, and associated with a fewer bacterial infections compared to historic controls. The efficacy of this prophylaxis strategy will best be determined in a planned randomized, placebo-controlled trial.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract The BuFluTBI conditioning regimen was designed with the primary goal of reducing non-relapse mortality (NRM) while maximizing primary disease control in patients ineligible for myeloablative ...conditioning. Patients with hematologic malignancies for whom limited long-term survival was expected with standard therapy were administered an outpatient conditioning regimen of busulfan 3.2 mg/kg IV on day −5, fludarabine 30 mg/m2 IV on days −4, −3, −2, and 200 cGy of total body irradiation (TBI) followed by stem cell infusion from related or unrelated donors. GVHD prophylaxis included cyclosporine and mycophenolate mofetil. 147 patients were enrolled from 2005-2011; 59% with myeloid disease and 41% with lymphoid disease. The median age was 64, and the median comorbidity index (HCT-CI) score was 3. Overall survival (OS), with 3.2 years median follow-up, was 60% at 1 year and 48% at 2 years, with projected OS 37% at 5 years. Relapse rates were 29% at 1 year and 33% at 2 years, with relapse mortality of 13% at 1 year, and 20% at 2 years. Nonrelapse mortality (NRM) at 1 year was 27% and 33% at 2 years. 54% of patients developed grade II-IV aGVHD and 67% of patients developed cGVHD within 2 years. On multivariate analysis, HCT-CI score 4 or greater, pre-transplant KPS less than 90, delayed platelet engraftment of more than 15 days, and grade II-IV aGVHD were found to be independent predictors of poor survival. There was no difference in OS or PFS between lymphoid and myeloid malignancies. BuFluTBI is an efficacious NMA regimen, active in both myeloid and lymphoid disease, and is ideally suited for use in patients age 65 and older or with an HCT-CI of 4 or greater.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: T cells can be activated and expanded ex vivo using the Xcellerate™ Process, in which peripheral blood mononuclear cells (PBMC) are incubated with anti-CD3 and anti-CD28 antibody-coated ...magnetic beads (Xcyte™-Dynabeads®). In an ongoing trial of Xcellerated T Cells in subjects with chronic lymphocytic leukemia, marked and sustained reductions in lymphadenopathy and splenomegaly were observed (Wierda et al., ASCO 2004). Increases in neutrophil, platelet and NK cell counts were also documented. This study is designed to determine if similar effects can be observed in subjects with indolent non-Hodgkin's lymphoma (NHL).
Methods: Subjects must have indolent NHL (follicular, small lymphocytic, marginal zone, or mantle cell lymphoma), have relapsed or refractory disease, and have received at least 1 but not more than 4 prior treatment regimens. PBMC are collected by leukapheresis for the Xcellerate Process, and subjects subsequently receive two infusions of 20–60 x 109 Xcellerated T Cells separated by 6–8 weeks. Approximately 40 subjects will be treated.
Results: Seven subjects have been enrolled and Xcellerated T Cells have been manufactured in 5 subjects to date. T cells expanded 181.8 ± 88.5 fold and the final product was >99.0 ± 0.0% T cells (mean + SD). One subject with small lymphocytic lymphoma has been treated with two infusions of 38.6 x 109 Xcellerated T Cells. There have been no serious adverse events to date. Following the first treatment, the lymphocyte count increased from 1.8 x 109/L to 2.9 x 109/L on Day 28. The neutrophil count also increased from 2.9 x 109/L to 5.5 x 109/L six weeks following infusion. The subject had a significant reduction in cervical lymphadenopathy and a slight decrease in bulky mesenteric lymphadenopathy six weeks following the first infusion.
Conclusions: Xcellerated T Cells can be manufactured in subjects with indolent NHL. Treatment leads to significant increases in T cell and neutrophil counts. Preliminary data suggest a reduction in peripheral lymphadenopathy. Data on additional subjects will be presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract We determined treatment-related mortality, progression-free survival (PFS), and overall survival (OS) after a second autologous HCT (HCT2) for patients with lymphoma relapse after a prior ...HCT (HCT1). Outcomes for patients with either Hodgkin lymphoma (HL, n = 21) or non-Hodgkin lymphoma (NHL, n = 19) receiving HCT2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were analyzed. The median age at HCT2 was 38 years (range: 16-61) and 22 (58%) patients had a Karnofsky performance score <90. HCT2 was performed >1 year after HCT1 in 82%. The probability of treatment-related mortality at day 100 was 11% (95% confidence interval CI, 3%-22%). The 1-, 3-, and 5-year probabilities of PFS were 50% (95% CI, 34%-66%), 36% (95% CI, 21%-52%), and 30% (95% CI, 16%-46%), respectively. Corresponding probabilities of survival were 65% (95% CI, 50%-79%), 36% (95% CI, 22%-52%), and 30% (95% CI, 17%-46%), respectively. At a median follow-up of 72 months (range: 12-124 months) after HCT2, 29 patients (73%) have died, 18 (62%) secondary to relapsed lymphoma. The outcomes of patients with HL and NHL were similar. In summary, this series represents the largest reported group of patients with relapsed lymphomas undergoing SCT2 following failed SCT1, and with long-term follow-up. Our series suggests that SCT2 is feasible in patients relapsing after prior HCT1, with a lower treatment-related mortality than that reported for allogeneic transplant in this setting. HCT2 should be considered for patients with relapsed HL or NHL after HCT1 without alternative allogeneic stem cell transplant options.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Since the beginning of allogeneic transplant procedures, isolation precautions have been used in an effort to prevent infectious complications. However, the medical benefit has been increasingly ...questioned and, given the substantial costs associated with each measure, practices have been subject to institutional variability. Recent examples from our own institution range from determining the needs for and planning the construction of a new clinical facility, to halting the spread of vancomycin-resistant Enterococcus (VRE), understanding the source of a parainfluenza outbreak, and analyzing the potential for delays in response time to acute emergencies while putting on contact isolation materials (gowns, masks, gloves, etc.). Standards for isolation may be subject to change when managing infection outbreaks or with new construction, and may be influenced by the changing financial pressures of the institution.
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FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
140.
Survivorship Hansen, Lisa; Hayes-Lattin, Brandon
Blood and Marrow Transplant Handbook
Book Chapter
The field of cancer survivorship has matured over the past 10 years, with research efforts coordinated by transplant societies, the National Cancer Institute’s Office of Cancer Survivorship, and ...patient advocate groups including the Lance Armstrong Foundation (http://www.livestrong.org). Most of these efforts have defined a cancer survivor as anyone living after a diagnosis of cancer, but the recommendations that follow will be directed at those survivors alive more than 1 year after transplantation.
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