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  • 21
    In: Blood, American Society of Hematology, Vol. 110, No. 7 ( 2007-10-01), p. 2744-2748
    Abstract: Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m2; n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 22
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3391-3391
    Abstract: Abstract 3391 Poster Board III-279 BACKGROUND: We previously reported on the outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in 24 patients (pts) with poor-risk multiple myeloma treated by Seattle Consortium Centers (Georges et al BBMT 2007). Here we update our observation to 43 pts with a median follow up of 3.3 years after allografting. PATIENTS: Pts with stage II-III MM (n=43) received AlloHCT at 9 centers between May 2000 and September 2008. Forty pts (93%) were matched with their donors for 10 of 10 HLA alleles, and 3 (7%) had single HLA-C allele-level mismatches. Median age at allotransplant was 53 (range 35–67) years. Median number of prior treatments was 2 (1–3), and median number of prior treatment cycles was 8 (5–22). All pts but 2 received at least 1 (range 1-3) high dose-Autograft regimen. Fifteen pts (35%) received planned tandem Auto/AlloHCT as consolidation to first line therapy. Allogeneic conditioning was with 2 Gy TBI plus fludarabine 90 mg/m2 and post allografting immunosuppression was with mycophenolate mofetil (MMF) and cyclosporine or tacrolimus. Disease status at allogeneic HCT included complete remission (CR, 6 pts, 14%), very good partial remission (VGPR, 12 pts, 28%), partial remission (PR, 14 pts, 33%) and refractory disease (RD, 11 pts, 26%). RESULTS: All pts had sustained donor engraftment. Twenty-eight (65%) developed grade 2 to 4 acute graft-versus-host-disease (GVHD) and 6 pts (14%) developed 3 to 4 acute GVHD. Twenty-six pts (60%) had extensive chronic GVHD. The overall response rate was 86%, with 18 pts (42%) achieving CR, 14 (33%) VGPR and 5 (12%) PR. With a median follow-up of 3.3 (0.3–8.1) years from allografting, median time to progression was 1.1 years. Median overall survival (OS) has not been reached. Median progression-free survival (PFS) was 1.5 years. Five-year estimated OS and PFS were 51% and 21% respectively. Cumulative incidence of nonrelapse mortality (NRM) at 100 days, 1 and 5 years were 2%, 16% and 19% respectively. The subgroup of 15 pts receiving upfront tandem Auto/AlloHCT had five-year estimated OS and PFS of 72% and 37%, respectively. These results are similar to the outcomes we observed in a series of 102 patients with MM who received upfront tandem Auto/AlloHCT from HLA-identical sibling donor (Rotta et al, Blood 2009) where five-year OS and PFS were 64% and 36%, respectively. CONCLUSION: The use of unrelated donors leads to sustained donor engraftment and is associated with a low 1-year NRM (16%). As consolidation of first remission, Tandem Auto/Allo HCT leads to similar 5-year outcomes as HCT from HLA-identical sibling donors. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 23
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2316-2316
    Abstract: We retrospectively analyzed data from 24 patients with chronic myeloid leukemia (CML) treated with HLA-matched related donor hematopoietic cell transplantation (HCT) after non-myeloablative conditioning with 2 Gy total body irradiation (TBI), given either alone (n=8) or in combination with 3 days of fludarabine, 30mg/m2/day (n=16). Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. CML patients in first chronic phase (CP1) (n=14), second chronic phase (n=4) or accelerated phase (n=6) who were not candidates for conventional HCT, were enrolled in a median of 28.5 (range, 11–271) months after diagnosis. The median age at HCT was 58 (range, 27–71) years. Unmodified G-CSF mobilized peripheral blood stem cell grafts containing medians of 7.9 (range, 2–18.1) x106 CD34+ cells/kg and 3.4 (range 1.7–2.4) x 108 CD3+ cells/kg, respectively, were infused. The median number of days in which ANC was less than 0.5 x 109/L was 5 (range, 0–8) days and 12 patients maintained ANCs greater than 0.5 x 109/L after HCT. Only 2 patients developed platelet counts less than 20 x 109/L. All patients had initial donor engraftment ( & gt;5% donor T-cell chimerism) at day 28 after transplant, and 17 (71%) achieved sustained full donor chimerism ( & gt;95% donor T-cell chimerism). There were 4 rejections followed by autologous hematopoietic reconstitution among 8 patients not given fludarabine, and donor lymphocyte infusions (DLI) were ineffective to reverse rejections. Fifteen (60%) patients achieved CR and 13 (54%) had complete molecular remissions, (defined as RT-PCR negativity for bcr-abl). Thirteen of 24 patients (54%) were alive and in CR at a median of 36 (range, 4–49) months after HCT. There were 5 (21%) deaths from non-relapse causes, one of them (4%) during the first 100 days. The incidences of grade II, III and IV acute GVHD were 38%, 4%, and 8%, respectively. The 2-year incidence of chronic extensive GVHD was 32%. The 2-year estimated overall survivals for patients in CP1 (n=14) and beyond CP1 (n=10) were 70% and 56%, respectively. Ten patients in CP1 received conditioning with fludarabine in addition to 2 Gy TBI; all ten achieved CR and 9 complete molecular remissions. Seven of 10 patients are alive in molecular remissions with a median follow-up of 36 (range, 6–49) months. In summary, non-myeloablative HCT were well tolerated in a group of patients who were older and/or medically infirm and therefore ineligible for myeloablative HCT. This approach should be considered for patients who fail to respond to initial conventional therapy and are not eligible for myeloablative conditioning regimens. The effectiveness of non-myeloablative compared to conventional myeloablative HCT will need to be definitively assessed in Phase III clinical trials.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 24
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 3450-3450
    Abstract: Abstract 3450 Objective: Allogeneic hematopoietic cell transplantation (HCT) following a variety of reduced-intensity conditioning regimens has been reported to produce encouraging results in patients with AML. In these studies disease relapse was the main cause of treatment failure, with 2–4 year relapse rates ranging between 32–61% resulting in overall survivals of 28–45% at 2–4 years. Our goal here was to examine whether pre-HCT variables could identify patients at high risk for relapse following nonmyeloablative allogeneic HCT, who thus would become candidates for additional interventions to reduce the risk of AML relapse. Methods: The data were derived from 274 consecutive Seattle Consortium patients (median age: 60 years) with de novo or secondary AML who underwent allogeneic HCT from related or unrelated donors after conditioning with 2 Gy total body irradiation (TBI) with or without fludarabine (90 mg/m2) as recently reported (Gyurkocza et al., JCO 2010 Jun 10;28(17):2859–2867). Cox regression was used to perform multivariate analysis of risk factors for relapse in a subset of 231 patients in morphologic leukemia-free state (defined as less than 5% marrow blasts) with (n=134) or without (n=97) peripheral blood cell count recovery (defined as platelets 〉 100,000/ml and neutrophils 〉 1,000/ml) at the time of HCT. In this multivariate model, AML beyond 1st complete remission (CR1), unfavorable cytogenetics (according to SWOG criteria), incomplete peripheral blood cell count recovery before HCT, and shorter time between diagnosis and HCT were associated with statistically significantly higher risk of relapse (Table 1). From this multivariate model we developed a relapse risk score that summarizes the contribution of multiple risk factors by assigning weights based on the relative magnitude of the log hazard ratios associated with the principal risk factors. From a starting score of 0, points were added or subtracted based on the following factors: 2nd CR: +1 point; 3rd or later CR: +2 points; unfavorable cytogenetics: +1 point; absence of pre-HCT peripheral blood cell count recovery: +0.5 points; time from diagnosis to HCT 〉 18 months, -2 points (Table 2). Patients were then stratified into 2 relapse risk groups according to whether the total risk score was ≤0 (low-risk) or 〉 0 (high-risk). Results: Stratification of patients according to the proposed Relapse Risk Score resulted in a clear separation of the two risk groups, with 5-year relapse rates of 50% and 17% in the high- and low-risk groups, respectively (Figure 1A). Five-year overall survival rates were 26% and 50% in the high- and low-risk groups, respectively (Figure 1B). Conclusion: Our Relapse Risk Score may be a useful tool to identify patients with AML at high risk for relapse, who could potentially benefit from additional interventions to reduce the risk of relapse following allogeneic HCT. We are currently attempting validation in an independent cohort of patients with AML to make this Risk Score more generalizable. Relapse/Progression (A) and Overall Survival (B) rates stratified by Relapse Risk Score. Disclosures: Off Label Use: Off label usage of fludarabine, cyclosporine, tacrolimus and mycophenolate mofetil is discussed.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 25
    In: British Journal of Haematology, Wiley, Vol. 143, No. 3 ( 2008-11), p. 395-403
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2008
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  • 26
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 149-149
    Abstract: We report the results of 256 patients (median age = 59; range, 5–74 years) with de novo AML in first complete remission (CR1; n=100), beyond CR1 (n=79) and with treatment-related or secondary AML (n=77) who underwent allogeneic hematopoietic cell transplantation (HCT) from HLA-matched related (n=109) or from unrelated donors (n=147). Indications of allogeneic HCT in CR1 were persistent cytogenetic or molecular evidence of disease, poor-risk cytogenetics at diagnosis, treatment-related or secondary AML and age more than 60 years. Younger patients were included if they had comorbid conditions that excluded them from conventional allogeneic HCT. Sixteen patients were mismatched with their donors for ≥ one HLA antigen, while the remainder were matched 10/10 at the antigen level. Conditioning consisted of low-dose total body irradiation (TBI; 2 Gy) on day 0 either alone (n=28) or combined with fludarabine, 30 mg/m2/day on days −4 to −2 (n=228). Calcineurin inhibitors (cyclosporine or tacrolimus) and mycophenolate mofetil were used for postgrafting immunosuppression. Durable engraftment was observed in 94% of patients. With a median follow-up of 35 (range, 3 – 111) months in surviving patients, the estimated progression-free and overall survivals at 5 years were 32% (95% CI: 25–38%) and 32% (95% CI: 25–38%), respectively. The cumulative incidences of relapse/progression and non-relapse mortality at 5 years were 40% (95% CI: 33–46%) and 29% (95% CI: 22–35%), respectively. Estimated 5-year survival rates, progression-free survival, relapse/progression rate, and non-relapse mortality according to disease status are shown in Table 1; Table 2 shows the same indices according to donor type. The cumulative incidences of grades II–IV and III–IV acute graft-versus-host disease (GVHD) in patients with related donors were 40% and 13%, and in those with unrelated donors were 58% and 14%, respectively. The cumulative incidence of chronic extensive GVHD at 5 years was 44% in patients with related donors, and 42% in patients with unrelated donors. Age & gt; 60 years at the time of HCT did not have an impact on the outcome (univariate analysis). Additional analyses regarding the impact of HCT comorbidity scores and minimal residual disease at the time of HCT are in progress. Based on this multicenter analysis, we conclude that allogeneic HCT from related or unrelated donors, utilizing a conditioning regimen of low dose TBI (2 Gy) with fludarabine provides long term remission in elderly and/or medically infirm patients with AML, who were not considered candidates for conventional HCT. Table 1. Estimated 5-year overall survival (OS), progression-free survival (PFS), relapse/progression rate (RR), and non-relapse mortality (NRM) according to disease status. CR1: 1st remission; & gt;CR1: subsequent remission, induction failure/persistent disease; sAML: treatment-related and secondary AML. Disease Status n %OS (95% CI) %PFS (95% CI) RR (95% CI) NRM (95% CI) CR1 100 33 (20–46) 34 (23–46) 36 (26–47) 30 (19–40) & gt;CR1 79 38 (26–49) 35 (23–46) 40 (29–52) 25 (15–35) sAML 77 20 (8–32) 23 (11–35) 45 (32–57) 32 (20–45) Table 2. Estimated 5-year overall survival (OS), progression-free survival (PFS), relapse/progression rate (RR), and non-relapse mortality (NRM) according to donor type. Donor Type n %OS (95% CI) %PFS (95% CI) RR (95% CI) NRM (95% CI) HLA-identical related 109 34 (23–44) 34 (24–45) 47 (37–58) 18 (10–26) HLA-matched unrelated 131 31 (22–40) 30 (21–39) 37 (29–46) 33 (24–72) HLA mismatched unrelated 16 24 (0–50) 24 (0–50) 6 (0–18) 70 (43–97)
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 27
    In: Blood, American Society of Hematology, Vol. 102, No. 9 ( 2003-11-01), p. 3447-3454
    Abstract: The full potential of a graft-versusmyeloma effect after allogeneic hematopoietic cell transplantation (HCT) for patients with multiple myeloma (MM) has not been realized because of excessive early transplantation-related mortality (TRM) with conventional HCT. Autologous HCTs have been characterized by almost universal disease recurrences. The current trial combined autologous HCT with subsequent nonmyeloablative allogeneic HCT to maintain the benefits of both approaches with acceptable toxicity. Fifty-four patients, 52 years of age (median; range, 29-71 years), with previously treated stage II or III MM (52% refractory or relapsed disease) were given melphalan 200 mg/m2 and autologous HC transplants. Regimen-related toxicities after autologous HCT were moderate with a median of 6 days of neutropenia, 7 days of hospitalization, and 1 death from infection. Forty to 229 days later (median, 62 days), 52 patients received a single fraction dose of 2 Gy total body irradiation and HC transplants from HLA-identical siblings with postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Patients experienced medians of 0 days of hospitalization, neutropenia, and thrombocytopenia. Sustained engraftment was uniform. With a median follow-up of 552 days after allografting, overall survival is 78%. One patient (2%) died before day 100 from disease progression. Thirty-eight percent of patients developed acute graft-versus-host disease (GVHD; grade II in all but 4 cases) and 46% chronic GVHD requiring therapy. Tumor responses occurred slowly. Thus far, 57% of patients have achieved complete remissions and 26% have achieved partial remissions for an overall response of 83%. Despite being evaluated in elderly patients with MM, this 2-step approach has reduced the acute toxicities of allogeneic HCT while achieving potent antitumor activities.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2003
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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