Addition of Rituximab to Mobilization and Conditioning Overcomes the Predictive Value of Follicular Lymphoma International Prognostic Index (FLIPI) Score in Patients with Relapsed FL Undergoing Autologous Stem Cell Transplantation (AUTO).

Abstract FLIPI is emerging as an important prognostic factor in patients (pts) with FL. In order to determine its significance in FL pts undergoing AUTO, we examined the outcome of 75 consecutive pts transplanted at the MD Anderson Cancer Center between 02/94 and 04/08. Pts were eligible if they had relapsed chemosensitive disease, and had no HLAidentical sibling donor. Twenty-nine pts were transplanted without rituximab (AUTO-R), and 46 pts received high-dose rituximab (AUTO+R) during stem cell mobilization and on days +1 and + 8 after transplantation as previously described (Khouri, JCO, 2005). Median age (range) at AUTO was 54 (33–76) and 49 (35–63) for the AUTO+R and AUTO-R groups respectively (P =0.002). FLIPI was determined at the time of transplantation; more patients had intermediate-high risk in AUTO+R than in AUTO-R (58% vs 27.5%, respectively, P = 0.011). Other patients characteristics were balanced for gender, time from diagnosis, histology subtypes (grades 1,2, 3a, and 3b), disease stage, LDH, bulk, B-symptoms, B-2microglobulin, bone marrow involvement, number of prior chemotherapy regimens received, remission status (CR vs PR), functional imaging, and co-morbidity score. Median follow-up (range) in months was 20 (1–88) for AUTO+R and 70 (4–167) for AUTO-R. Progression-free survival (PFS) was significantly different between AUTO+R and AUTO-R (P = 0.004), with estimated three-year PFS of 48% for AUTO-R and 79% for AUTO+R. Using Cox proportional hazards regression models, the # of prior chemotherapy regimens received (<3 vs >/=3) (P = 0.015) was the only factor associated with PFS in the AUTO+R group, whereas both age (P=0.010), and risk based on FLIPI (P=0.019) were independently associated with PFS in the AUTO-R group. Pts with low-risk vs. intermediate/high-risk had three-year PFS of 62% and 13%, respectively, in the AUTO-R group, whereas in the AUTO+R group, three-year PFS was 90% and 76% in the low-risk and intermediate/high-risk pts, respectively (Figure). Conclusions: These results suggest that the addition of R to the mobilization and conditioning improves the outcome in pts with relapsed chemosensitive FL treated by AUTO. The number of prior chemotherapy regimens received rather than FLIPI score is the most important determinant of outcome in this setting. Figure Figure

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Allogeneic and Autologous Transplantation In Patients with Aggressive B- and T-Cell Lymphomas

Blood ◽

10.1182/blood.v116.21.3544.3544 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3544-3544

Author(s):

Frank Schueler ◽

Madelaine Hoffmann ◽

Christian Pfrepper ◽

Said Daneschnejad ◽

Thoralf Lange ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

Autologous Transplantation ◽

B Cell Lymphoma ◽

Disease Stage ◽

High Dose ◽

Prior Chemotherapy ◽

T Cell Lymphomas

Abstract Abstract 3544 The prognosis of patients with aggressive relapsed or refractory B- or T-cell lymphomas is poor with conventional chemotherapy. Therefore, high-dose chemotherapy followed by autologous or allogeneic transplantation is the treatment of choice in these patients. We investigated the outcome of patients with aggressive B- or T-cell lymphomas transplanted between 1998 and 2009 in one centre. A total of 104 patients with diffuse large B-cell lymphoma (DLBCL) (n=69) and T-lymphoblastic lymphoma (T-LBL) (n=35) received autologous (auto) (n=66; DLBCL: 68%; T-LBL: 32%) or allogeneic (allo) (n=38; DLBCL: 63%; T-LBL: 37%) HSCT. Patients ineligible for auto transplantation, who did not respond to prior chemotherapy or had bone marrow involvement, were assigned to allo transplantation. Allo HSCT recipients were more likely to have high risk disease (higher disease stage, more prior chemotherapy regimens, resistant disease). Recipients of auto HCT were more likely to have chemosensitive disease at HSCT compared to patients at allo HCT (70% vs. 30%). Median age at transplantation was 52 years for auto and 42 years for allo HSCT. Median follow up was 12.7 (0.2-106) months after auto and 6.4 (0.4-111) months after allo transplantion. All patients with auto HSCT received BEAM and patients with allo HSCT TBI-based preparative regimen (myeloablative: n=23; reduced intensity: n=15). In the cohort of 104 patients the estimated 5-years overall (OS) and progression free survival (PFS) were 38% and 44%, respectively. There was no difference in OS and PFS between DLBCL and T-LBL (p=0.44). The estimated OS and PFS after allo HCT were significant lower (25% and 37%) than after auto HCT (45% and 47%; p=0.008 and p=0.03) caused by outcome differences in patients with DLBCL (p=0.02). Interestingly, OS and PFS were not different in patients with T-LBL transplanted with auto or allo HSCT (p=0.55 [OS] and p=0.34 [PFS]). The estimated PFS was significantly better in chemosensitive than chemorefractory patients (p=0.0001), however the OS and PFS were similar in chemosensitive group of patients regardless auto or allo HSCT (PFS: 50% vs. 51%; p=0.57; OS: 49% (auto) vs 32% (allo); p=0.19). Treatment related mortality (TRM) at day 100 was 18% after allo HSCT compared to 8% after auto. In conclusion, allo HSCT in patients with aggressive B- or T-cell lymphoma ineligible for auto transplantation is an attractive treatment option for these patients with high risk of relapse with a considerably low TRM. The response status at the moment of HSCT is the most important parameter affecting either OS or PFS. Disclosures: Niederwieser: Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau.

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Reduced Intensity Conditioning (RIC) Regimen Followed by Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Adult Patients with Acute Lymphoblastic Leukemia (ALL)

Blood ◽

10.1182/blood.v112.11.4326.4326 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4326-4326

Author(s):

Leandro de Padua Silva ◽

Rima M. Saliba ◽

Sergio Giralt ◽

Marcos De Lima ◽

Chitra Hosing ◽

...

Keyword(s):

Stem Cell ◽

Median Time ◽

Cumulative Incidence ◽

Lymphoblastic Leukemia ◽

Chronic Gvhd ◽

Disease Stage ◽

Hematopoietic Stem ◽

Cell Dose ◽

Morbidity Score ◽

Co Morbidity

Abstract Background: RIC regimens are less myelosuppressive, but remain adequately immunosuppressive, allowing for successful engraftment with acceptable treatment-related mortality (TRM) in older or more frail patients (pts) who otherwise would not be suitable candidates for HSCT. This is particularly relevant in ALL, since pts often sustain toxicity from dose-intense upfront regimens or may be diagnosed in advanced age. The antitumor effect of this approach is not well-established in ALL. Methods: We evaluated outcomes of 30 advanced ALL pts (19 M/11 F) treated from August 1996 to May 2008 with FM140 (fludarabine 120 mg/m2, melphalan 140 mg/m2) and unmanipulated stem cells. Graft vs. host disease (GVHD) prophylaxis consisted of tacrolimus and mini-dose methotrexate in all but 1 pt who received cyclosporine. Anti-thymocyte-globulin was added to matched unrelated pts. Results: The median age was 44 years (range 23–64). ECOG performance status at time of HSCT was 0 (n=16), 1 (n=10) or 2 (n=4) with median co-morbidity score of 3 (range 0–7) by Charlson Comorbidity Index (CCI). Twenty-four pts had B-lineage and 6 had T-lineage disease. Cytogenetic data were available for 26 pts; 19 had high-risk cytogenetics, including 9 with Ph+ disease. Disease stage at time of study entry was CR1 (n=5), ≥CR1 (n=12), or primary or refractory relapse (n=13), with median 2 prior chemotherapy regimens (range 1–4); five pts had a prior allogeneic HSCT. Donor type was matched related (n=13) or matched unrelated (n=17) and stem cell source was bone marrow (n=14) or peripheral blood (n=16). The median total nucleated cell dose and CD34+ cell dose were 3.80 × 108 cells (range 0.68–17.16) and 4.15 × 106 cells (range 1.78–12.03), respectively. Median time to ANC 0.5 × 109/L was 13 days (range 10–24). Median time to platelet count 20 × 109/L was 18 days (range 10–57). Eight pts were alive at a median follow up of 12 months from HSCT (range 3–59). OS and DFS were 32% and 29%, respectively, at 1 year. Of note, only 1 among 5 pts in CR1 had disease progression, compared to 8 among 13 with refractory disease at time of HSCT. The cumulative incidence of acute GVHD, grades II–IV and III–IV were 40% and 13%, respectively, and chronic GVHD was 22% (7% for extensive). The cumulative incidence of TRM at 100 days and 1 year were 17% and 33%, respectively. Among 22 deaths, 14 were related to disease recurrence, 4 related to infection and 4 related to GVHD. Conclusion: RIC HSCT can provide disease control in patients with ALL, and merits further evaluation. Alternative treatment strategies need to be explored in pts with advanced disease. The observed TRM rate is comparable to what has been previously reported for this regimen in heavily pretreated leukemia patients.

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A Disease and Stage Risk Grouping System for Patients Undergoing Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood.v118.21.327.327 ◽

2011 ◽

Vol 118 (21) ◽

pp. 327-327

Author(s):

Philippe Armand ◽

Christopher J Gibson ◽

Corey Cutler ◽

Vincent T Ho ◽

John Koreth ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Risk Groups ◽

Low Risk ◽

Disease Stage ◽

Reduced Intensity Conditioning ◽

T Cell Lymphomas ◽

Risk Grouping ◽

Reduced Intensity

Abstract Abstract 327 Background: The outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) varies significantly based on the patients' disease and stage at the time of HSCT. When analyzing outcomes of HSCT in heterogeneous patient populations, whether in retrospective or prospective studies, it is therefore necessary to stratify patients based on their disease/stage risk. At present, there is no robust method for doing so; the most commonly used breakdowns are based on older data that may not be applicable today, and do not incorporate cytogenetics for myeloid diseases, which are an important prognostic factor. Methods: We analyzed a cohort of 1539 patients transplanted between 2000 and 2009 at Dana-Farber/Brigham and Women's Hospital, and reviewed their disease type (including cytogenetics) and stage at HSCT. Based on proportional hazards modeling for overall survival (with a median follow-up of 35 months), we defined disease and stage risk groups, with independent analyses performed in the 812 patients who underwent myeloablative conditioning (MAC) and the 727 who underwent reduced intensity conditioning (RIC). We used the results to define overall disease/stage risk groups for both MAC and RIC HSCT. Results: Interestingly, the disease risk groups turned out to be identical for MAC and RIC; the stage risk groups were very similar, except for the assignment of CR>1 to low risk in MAC but high risk in RIC. The groups were as follows: Low-risk disease: AML with favorable cytogenetics, CLL, CML, Hodgkin lymphoma, and non-Hodgkin lymphoma (excluding extranodal T-cell lymphomas) Intermediate-risk disease: ALL, AML or MDS with intermediate cytogenetics, myeloproliferative neoplasms, and multiple myeloma High-risk disease: AML or MDS with adverse cytogenetics, extranodal T-cell lymphomas Low-risk stage: CR1, CR>1 (for MAC), PR1, untreated disease, CP CML High-risk stage: CR>1 (for RIC), PR>1, induction failure or active relapse, accelerated or blast phase CML Those groups could be combined to form 4 overall groups with highly significantly different OS and PFS (Table and Figure). Conclusion: We propose a disease/stage risk grouping scheme for patients undergoing HSCT, applicable to both myeloablative and reduced intensity conditioning transplantation, which separates patients into 4 groups with significantly different OS and PFS. This scheme could be used for prognostic purposes, and to stratify patients in retrospective studies or in clinical trials. In the future, it may be further validated and refined through registry studies. Disclosures: No relevant conflicts of interest to declare.

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