scholarly journals Allogenic Stem Cell Transplantation for Secondary CNS Lymphoma: A Retrospective Review of 21 Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3342-3342 ◽  
Author(s):  
Cole Sterling ◽  
Nina D. Wagner-Johnston ◽  
Douglas E Gladstone ◽  
Richard F. Ambinder ◽  
Lode J. Swinnen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Residual Disease ◽  
Cns Lymphoma ◽  
P Value ◽  
Myeloablative Conditioning ◽  
Advisory Committees ◽  
Term Survival ◽  
Cns Disease ◽  
Post Transplant

INTRODUCTION: Allogeneic blood or marrow transplant (alloBMT) is widely used in relapsed/refractory systemic non-Hodgkin lymphoma. The graft-versus-tumor effect has been thought to be blunted by the immune privilege of the central nervous system (CNS). Communication between the CNS and the systemic immune system suggests that CNS disease could benefit from the graft versus lymphoma (GVL) effect provided by alloBMT. METHODS: The charts of all patients who received post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis between January 2004 and October 2018 were reviewed. Survival statistics were calculated using the Kaplan-Meier method. Differences in time to death between groups were estimated using Cox proportional hazards models. RESULTS: Twenty-one patients with systemic lymphoma involving the CNS were identified. The median age was 59 years (range 24-73); 7 were over the age of 60 and 13 were male. Histology types included diffuse large B cell (71%), Burkitt (10%), T cell (10%), follicular (5%), and anaplastic large cell (5%). Prior to transplant, 12 patients were in complete remission, 9 had residual disease, and 5 had residual CNS disease by imaging. Induction therapy included CNS radiation therapy in 11 of 21 patients (52%) and high-dose methotrexate (HD-MTX) in 10 (48%). Only 1 patient was in first remission, with the remaining 20 in second or later remission. All but 1 patient received non-myeloablative conditioning using fludarabine, cyclophosphamide, and total-body irradiation; the other patient received busulfan and cyclophosphamide. Fifteen patients (71%) had haploidentical donors. Graft source was bone marrow in 18 patients and G-CSF-stimulated peripheral blood in 3. Median overall survival (OS) for the entire cohort was 1375 days (95% confidence interval [CI] 184-NR) and median progression free survival (PFS) was 1375 days (95% CI 112-NR). Three-year overall survival was 51% (95% CI 27-71%). The cumulative incidence of relapse was 29% (95% CI 9-49%) at 3 years, and non-relapse mortality was 20% (95% CI 2-38%) at 1 year. Of the 6 patients who relapsed, 2 were CNS only, 2 were systemic only, and 2 were combined CNS / systemic. There were 2 cases of grade III-IV acute GVHD and 1 case of chronic GVHD involving the mouth. Univariable analysis revealed no predictors of survival in our small data set: age > 60 (hazard ratio [HR] 1.48, 95% CI 0.42-5.29, p-value 0.54), haploidentical donor (HR 4.2, 95% CI 0.53-33.66, p-value 0.17), residual disease (HR 1.3, CI 0.37-4.52, p-value 0.68), and prior CNS radiation (HR 1.5, 95% CI 0.42-5.31, p-value 0.53). DISCUSSION: Allogeneic BMT with non-myeloablative conditioning is potentially curative in patients with secondary CNS lymphoma. Post-transplant cyclophosphamide is well tolerated in this older group. Myeloablative conditioning directed at the CNS is not required for long-term survival. Given its biologic plausibility and potential as a viable treatment option in certain patient populations, the role of alloBMT in CNS lymphoma deserves further investigation. Figure Disclosures Wagner-Johnston: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Jannsen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Swinnen:Pharmacyclics: Consultancy; AbbVie: Consultancy.

Reduced Severe aGVHD and Improved Survival Using Post Transplant Cyclophosphamide/Tacrolimus/Methotrexate Graft Versus Host Disease Prophylaxis in AML Patients Receiving Myeloablative Fractionated Busulfan Conditioning Regimen

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3296-3296
Author(s):  
Uday Popat ◽  
Rima M. Saliba ◽  
Rohtesh S. Mehta ◽  
Amanda L. Olson ◽  
Julianne Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Similar Proportion ◽  
Myeloablative Conditioning ◽  
Advisory Committees ◽  
Post Transplant ◽  
Gvhd Prophylaxis

Background: Myeloablative conditioning can be given safely to older patients by simply administering busulfan over a longer period (fractionated busulfan regimen) than the standard four day regimen. (Popat et al Lancet Haematology 2018). Subsequently, we added post-transplant cyclophosphamide (PTCy) GVHD prophylaxis to our fractionated regimen with a hypothesis that it will reduce GVHD and improve outcomes. Herein, we report the results of our retrospective analysis comparing outcomes of patients with AML who received fractionated busulfan myeloablative conditioning and PTCy versus standard tacrolimus (Tac) and methotrexate (Mtx) GVHD prophylaxis. Methods: Patients with AML between 18-70 years of age with adequate organ function and 8/8-HLA matched related or unrelated donor, who were treated on 4 consecutive protocols using fractionated busulfan were included in the analysis. All patients received two fixed doses of busulfan 80mg/m2 as outpatient either on days -13 and -12, or on days -20 and-13 followed by busulfan on day -6 to -3 dosed to achieve target area under the curve (AUC) of 20,000 mol/min for the whole course based on pharmacokinetic studies. Fludarabine ± cladribine were given on day -6 to -3. GVHD prophylaxis was PTCy 50mg/kg on days 3 and 4 and Tac ± mycophenolate mofetil in PTCy cohort (n=53), or standard Tac+ Mtx (n=53). Patients in both the cohorts were matched 1:1 by propensity score. Results: Baseline characteristics were similar between the PTCy and Tac/Mtx cohorts. The median age was 60 (range, 18-70) and 58 (range, 24-70) years, respectively, (P=0.3). Forty-nine percent were in CR, and 30% had comorbidity index >3 in each arm. Similar proportion of patients had ELN adverse risk in both arms (43% vs 40%, respectively P=0.7). The median follow up was 19 months (range, 3-36) in the PTCy and 46 months (range, 14-73) in Tac/Mtx cohort. Overall survival at 2-year was 78% vs 58% (P=0.03), non-relapse mortality was 6% vs 13% (P=0.2), incidence of grade 3-4 acute GVHD at 1-year was 6% vs 19% (P=0.07) and chronic GVHD at 2-year was 10% vs 29% (P=0.03) [Table 1 and figure 1]. The median time to neutrophil engraftment was prolonged by 3 days (15 vs 12 days; P<0.001) and platelet engraftment by 9 days (22 vs 13 days; P<0.001) in the PTCy cohort. Full donor chimerism at day 30 was noted in 79% vs 28% in the PTCy and Tac/Mtx cohorts respectively, (P<0.001). Conclusion: As compared to Tac/Mtx, PTCy-based GVHD prophylaxis not only reduced severe acute GVHD and chronic GVHD, but also improved overall survival in AML patients up to the age of 70 years who received myeloablative fractionated busulfan conditioning. Prospective randomized trial is warranted to validate these findings. Disclosures Popat: Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Ciurea:Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder; MolMed: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding. Kebriaei:Kite: Honoraria; Pfizer: Honoraria; Amgen: Research Funding; Jazz: Consultancy. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Oran:Astex pharmaceuticals: Research Funding; AROG pharmaceuticals: Research Funding. Qazilbash:Genzyme: Other: Speaker; Amgen: Consultancy, Other: Advisory Board; Autolus: Consultancy; Bioclinical: Consultancy. Molldrem:M. D. Anderson & Astellas Pharma: Other: Royalties. Champlin:Johnson and Johnson: Consultancy; Actinium: Consultancy; Sanofi-Genzyme: Research Funding.

scholarly journals Female Gender Is Associated with Improved Long-Term Survival Following Allogeneic Hematopoietic Stem Cell Transplant

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Prioty Islam ◽  
Haesu Jin ◽  
Felicia Cao ◽  
Lauren M. Bohannon ◽  
Yi Ren ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Board Of Directors ◽  
P Value ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Term Survival ◽  
Patient Gender ◽  
Long Term Survivors

Introduction: Life expectancy for long-term survivors of allogeneic hematopoietic stem cell transplant (allo-HCT) is significantly lower compared to that of the age-matched general population, despite a relatively low primary disease relapse rate &gt;2 years post-transplant. Long-term transplant-related complications instead account for most mortality in this patient population. These include chronic graft-versus-host disease (cGVHD), infection, organ failure, and secondary cancers. In addition, gender is emerging as a critical determinant of outcome in the immediate post-transplant setting. However, less is known regarding gender effects on outcomes of long-term survivors. We retrospectively investigated the impact of recipient gender and donor-recipient gender mismatch on outcomes of long-term survivors of allo-HCT. Methods: We performed a retrospective analysis using Duke University's Adult Blood and Marrow Transplant database, supplemented by individual patient chart review. Inclusion criteria consisted of long-term survivors of first allo-HCT, excluding syngeneic, between 1995 - 2015 for a hematologic malignancy. A long-term survivor is defined as having been alive with documented follow-up to at least five years following allo-HCT. Patient characteristics were summarized as count (%) for categorical variables and median (interquartile range) for continuous variables. Fisher's exact tests or t-tests were used to compare difference between groups. Overall survival was estimated using the Kaplan-Meier method and multivariable Cox proportional hazard model. Patients who had received cord blood allograft were excluded from donor-recipient gender survival analyses. SAS version 9.4 (SAS Institute, Cary, NC) and R 3.5.0 were used to perform statistical analyses. Results: Over this 20-year period, 1103 patients underwent allo-HCT, with 247 (22%) meeting inclusion criteria. Of these 247, males and females had similar demographic and treatment characteristics (Table 1). However, significantly more deaths after the 5-year landmark occurred in male recipients (Figure 1, p value=0.003). To estimate whether this was due to the general population-wide shorter life expectancy for males, we performed Kaplan-Meier estimates of survival for patients aged &lt; 50 years at transplant and aged ≥ 50 years at transplant, with similar results for both groups (Figure 2, p value=0.006). Interestingly, donor gender did not have a significant impact on overall survival in multivariate analysis (Table 2), and differences in overall survival of donor-recipient gender pairs was driven by patient gender (Figure 3, p value =0.007). A separate multivariate analysis of interaction between donor-recipient gender pairs further demonstrated that significant differences in overall survival were due to patient gender (Table 3). In addition to patient gender, only cGVHD retained significance as a covariate with impact on overall survival in multivariate analysis (Table 2, Table 3). Men experienced slightly higher rates and increased severity of cGVHD, and a greater percentage of cGVHD-related mortality as compared to females, though these findings were not statistically significant (Table 1). Conclusion: In this long-term survival analysis of allo-HCT adult patients, one of the only to include follow-up to 15 years, our results show that women survive significantly longer than men irrespective of their age at transplant. This outcome is independent of other common pre-transplant prognostic indicators such as donor gender or performance status at transplant. Inferior survival for males is consistent with survival outcomes described in another large and fully risk annotated HCT cohort, and in solid organ transplants such as lung and kidney. Gathering evidence suggests a biologic basis for long-term gender-determined outcomes, possibly due to differing rates or severity of cGVHD or sustained alloimmune tolerance in females. Male patients should be counseled on their possible increased long-term risk. Prospective and larger studies are warranted to validate these retrospective clinical results. Disclosures Rizzieri: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; abbvie: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Acrobiotech: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Minimal Residual Disease Eradication with Venetoclax in Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-14
Author(s):  
Alexander Coltoff ◽  
Joseph G. Jurcic ◽  
Peter Campbell ◽  
Daniel J. Lee ◽  
Mark L Heaney ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Median Overall Survival ◽  
Residual Disease ◽  
Institutional Research ◽  
Negative Group ◽  
Advisory Committees ◽  
Research Grants

Introduction The combination of the BCL-2 inhibitor venetoclax with an HMA (HMA/Ven) has improved outcomes in previously untreated patients with AML not eligible for intensive induction therapy. In a phase Ib study, 67% of patients achieved a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) with a median overall survival (OS) of 17.5 months (DiNardo CD et al. Blood 2019; 133(1):7-17). HMA/Ven has also demonstrated efficacy in a heavily pretreated population with relapsed or refractory (R/R) AML, the majority of whom had prior HMA exposure (DiNardo CD et al. Am J Hematol 2018; 93(3):401-7). Measurable residual disease (MRD) is recognized as an independent prognostic indicator important for risk stratification and treatment planning (Schuurhuis GJ et al. Blood 2018; 131(12):1275-91). To date, however, there have been few reports on the effect of HMA/Ven on MRD. Methods This is a retrospective case series of patients with AML at a single-center tertiary-care institution. Patients ≥ 18 years of age who were treated with HMA/Ven between January 2017 and June 2020, either in the upfront or salvage setting, for AML were included. Outcomes included CR/CRi rate, MRD response, relapse free survival (RFS), and OS. MRD was assessed via multicolor flow cytometry with a sensitivity of 10-3 (0.1%). Results Nineteen patients were identified, 12 (63%) of whom were female. The median age at the time of HMA/Ven initiation was 71 years (range, 21 - 87 years). Ten (53%) patients had de novo AML and 9 had secondary or therapy-related AML. By 2017 ELN criteria, 3 (16%) patients had favorable-risk, 9 (47%) had intermediate-risk, and 7 (37%) had adverse-risk AML. Nine (47%) patients had R/R AML; 5 received HMA/Ven as first salvage therapy, and 4 as 2nd or greater salvage. Three (16%) patients had prior HMA exposure. No patient had prior venetoclax exposure. Median follow-up was 9.1 months (range, 1-21.1 months). Ten (53%) patients received azacitidine and 9 (47%) were given decitabine. Venetoclax doses ranged from 50 to 400 mg daily, depending on participation in a clinical trial and concomitant medications. Eight patients achieved a CR and 7 patients achieved a CRi for a combined CR/CRi rate of 79%. The CR/CRi rate was 90% (9/10) in the upfront setting, and 66% (6/9) in the salvage setting. The median time and number of cycles to best clinical response was 2.3 months (range, 0.9-3.9 months) and 2 (range, 1-3 cycles), respectively. Eleven (73%) of the 15 responders achieved MRD clearance after a median of 2 cycles (range, 1-3 cycles) (Table 1). Two of 4 (50%) MRD-positive patients relapsed, while 4 (36%) of 11 MRD-negative patients relapsed (Figure 1). Relapse occurred at a median of 2.0 months (range, 1.3-2.7 months) in the MRD positive group and 11.0 months (range, 2.8-14 months) in the MRD negative group. One patient died of infectious complications while MRD negative. Three patients, all of whom were treated for R/R disease, proceeded to an allogeneic stem cell transplant (HSCT). Two were MRD negative at the time of HSCT and all remained in remission. At the time of data cutoff, 7 (64%) of 11 MRD-negative patients were alive, and all 4 MRD-positive patients were alive. Causes of death in the MRD-negative group included disease relapse (3 patients) and infection (1 patient). Median overall survival in the entire cohort (range, 32 days-NR) was not reached. Conclusions HMA/Ven was highly effective as both upfront and salvage therapy. Surprisingly, the salvage CR/CRi rate in this series was 66%, allowing half of the responders to proceed to HSCT. The majority (73%) of responders achieved MRD negativity. While MRD status influenced RFS, 36% of MRD-negative patients relapsed. Additionally, the same percentage of MRD-negative patients died during follow-up, versus none of the patients with MRD-positivity. This indicates the need for more sensitive methods to assess MRD and for novel therapeutic strategies to eliminate MRD, thereby improving long-term outcomes. Larger prospective studies are needed to define the role of MRD assessment with venetoclax-containing regimens. Disclosures Jurcic: AbbVie:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Syros Pharmaceuticals:Research Funding;PTC Therapeutics:Research Funding;Arog Pharmaceuticals:Research Funding;Kura Oncology:Research Funding;Forma Therapeutics:Research Funding;Astellas:Research Funding;Genentech:Research Funding;Novartis:Consultancy, Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS:Consultancy, Research Funding.Campbell:AstraZeneca:Consultancy.Lee:Genentech:Research Funding;Sumitomo Dainippon Pharma Oncology, Inc.:Research Funding;AbbVie:Research Funding;Novartis:Research Funding;Bayer:Research Funding;Celgene:Consultancy;Forty Seven:Research Funding.Heaney:Blueprint Medicines Corporation:Research Funding;BMS:Research Funding;CTI Biopharma:Consultancy, Research Funding;Deciphera:Research Funding;Incyte:Research Funding;Novartis:Consultancy, Research Funding;Sierra Oncology:Research Funding;AbbVie:Consultancy;Partner Therapeutics:Consultancy.Lamanna:Janssen:Consultancy, Membership on an entity's Board of Directors or advisory committees;Octapharma:Research Funding;Juno:Other: Institutional research grants, Research Funding;Gilead:Consultancy, Membership on an entity's Board of Directors or advisory committees;Astra Zeneca:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Pharmacyclics:Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Bei-Gene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Abbvie:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Oncternal, Verastem, TG Therapeutics:Other: Institutional research grants, Research Funding;MingSight:Other: Institutional research grants, Research Funding;Loxo:Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees;Columbia University Medical Center:Current Employment.

Hypogammaglobulinemia during Rituximab Maintenance after Transplantation Is a Surrogate Marker for Disease Control in Patients with Mantle-Cell Lymphoma, an Analysis from the LyMa Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-42
Author(s):  
Louise Bouard ◽  
Catherine Thieblemont ◽  
Krimo Bouabdallah ◽  
Thomas Gastinne ◽  
Anne Moreau ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Disease Control ◽  
Board Of Directors ◽  
Research Funding ◽  
P Value ◽  
Immune Recovery ◽  
Advisory Committees ◽  
Post Transplant ◽  
Rituximab Maintenance ◽  
Mantle Cell

Introduction Rituximab maintenance (RM) (375mg/m2 per infusion every 2 months for 3 years) in transplanted patients with mantle-cell lymphomas (MCL) prolongs disease control (LyMa trial, Le Gouill et al NEJM; NCT00921414). However, post-transplant RM might also induce long-term immune deficiency and thus increases risk of infection. To address these issues, we performed an ancillary pre-planned study based on the LyMa trial, a phase III trial that compared RM versus observation (Obs) after ASCT in MCL patients. We compared post-transplant immune-deficiency and its impact on PFS and OS in the RM vs Obs groups. Method All transplanted and randomized patients enrolled in the LyMa trial were eligible for the present study. The following data were collected during the post-ASCT period and monitored according to protocol procedure: febrile event, clinically documented infection, hospitalization for infection, neutropenia, hypogammaglobulinemia and T CD4 lymphocytes count. We also retrospectively collected the use of immune globulin (Ig) substitution. In the LyMa trial, patients were randomized between RM vs Obs after transplantation. To decipher the implication of ASCT or RM in immune recovery, treatment periods were divided in 4: &lt; 6 months after randomization, from 6 to 12 months after randomization, from one to two year after randomization, and from 2 to 3 years after randomization (respectively periods A, B, C and D). Chi-square or Fisher's exact tests were used as appropriate to investigate differences between arms in each treatment period. For all tests, a two-sided p-value&lt;0.05 was considered statistically significant Results 240 patients were eligible, 120 in each arm. Patients' characteristics at diagnosis and inclusion were similar in the two arms. Number of hospitalizations due to infections was not statistically different in RM vs Obs in all periods. As previously shown, grade 3/4 infections incidence did not differ in the 2 arms. However, febrile events were more frequent in the RM arm (32 pts vs 11; 38 events vs 12) but this was statistically significant only in C and D periods; p=0,03 for the 2 periods. In all, 51 infections in 44 pts were reported in Obs vs 127 events in 82 pts in RM arm. This difference was also only statistically significant during the C period, p=0,001. Grade 4 neutropenia incidence and T CD4 count did not differ between the two arms in all tested periods. Hypogammaglobulinemia was statistically more frequent in RM during C and D periods (p=0,0001 and p&lt; 0,0001, respectively). Mean level of gammaglobulinemia on D period was 6,50 g/L (range 0,6-11,7) in obs arm versus 4,99 (range 1,0-9,5) in RM arm (p&lt; 0,0001). 36 pts in RM arm vs 10 pts in obs arm were substituted with Ig and the difference was statistically significant only in period D, p&lt;0,0001. Febrile and infectious episodes; neutropenia and T CD 4 lymphopenia did not modify PFS and OS. Patients with gammaglobulinemia &lt; 6g/L in RM arm and in the whole cohort had longer PFS compared to pts who did not present hypogammaglobulinemia : 3-years PFS 93,2% vs 63,5% in RM arm HR = 0,294, 95% CI (0,113-0,767 and), p=0,01 and 3-years PFS 85,6% vs 63,6% in the whole cohort, HR adjusted on treatment arm=0,488 95% CI (0,287-0,830), p=0,008 . PFS was not modified by gammaglobulin level in the Obs arm and it did not modified OS in both arms. We performed a multivariate analysis to determine which data were predictive of infectious events and delayed immune recovery (neutropenia, hypogamma, T CD 4 lymphopenia). This included all univariate parameters with p value &lt; 0,2, among clinical and biological characteristics at diagnosis, response after induction and number of rituximab injections. Interestingly, among others expected parameters, complete response assessed by TDM was predictive of hypogamma with Odd Ratio 2,972 (1,263-6,994) p=0,0126. No value was predictive of neutropenia or T CD4 cytopenia. Conclusion As compared to observation, the use of post-transplant RM does not increase risk of neutropenia and T CD4 lymphopenia. However febrile and infectious events, hypogammaglobulinemia and Ig substitution are more frequent after one year post transplantation. Hypogamma &lt; 6g/L is associated with longer PFS and complete morphologic response. This suggests that hypogammaglobulinemia could be a surrogate for disease response quality and duration. Our findings deserve to be confirmed. Disclosures Thieblemont: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Hospira: Research Funding; Cellectis: Speakers Bureau; Janssen: Honoraria; University Employement: Current Employment. Bouabdallah:Gilead Sciences: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Oberic:Roche, Janssen: Other: Travel, Accommodations, Expenses; Roche: Honoraria; Roche, Janssen: Consultancy. Hermine:AB Science: Consultancy, Current equity holder in publicly-traded company, Honoraria, Patents & Royalties, Research Funding; Celgene BMS: Consultancy, Research Funding; Novartis: Research Funding; Alexion: Research Funding; Roche: Consultancy. Le Gouill:Loxo Oncology at Lilly: Consultancy; Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria.

Post-Transplant Platelet Recovery Kinetics and Its Association with Overall Survival in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2049-2049
Author(s):  
Jie Li ◽  
Jillian Alyse Deppa ◽  
Zahir Ali ◽  
Michael Graiser ◽  
Amelia Langston ◽  
...  
Keyword(s):  
Overall Survival ◽  
Platelet Count ◽  
Early Death ◽  
Disease Status ◽  
P Value ◽  
Term Survival ◽  
Allogeneic Hsct ◽  
Post Transplant ◽  
Platelet Counts

Abstract Abstract 2049 Background: Post-transplant thrombocytopenia is universal among recipients of hematopoietic stem cell transplantation (HSCT). We have previously reported a secondary post-transplant thrombocytopenia following autologous HSCT which is associated with poor survival (Ninan MJ, et al., BBMT 2007), however the clinical significance of a fall post-engraftment in platelet counts among recipients of allogeneic HSCT has not been studied. Methods: A total of 929 consecutive pts who underwent allogeneic HSCT between 1993 and 2009 were studied in an IRB-approved retrospective analysis. 55% of pts were male and 45% were female with a median age of 43 ± 12.6 years. Diagnoses included: acute leukemia (423, 46%), chronic leukemia (197, 21%), non-Hodgkin's lymphoma (110, 12%),myelodysplastic syndrome (93, 10%), multiple myeloma (26, 3%), and other less common malignancies (80, 8%). Disease status was classified into five different categories: complete remission (287, 31%), partial remission (297, 34%), refractory (180, 19%), untreated (28, 3%) and incompletely classified (137, 15%). Grafts were obtained from related donors in 595 pts (64%), and unrelated donors in 334 pts (36%), with 55% peripheral blood stem cell (PBSC), 42% bone marrow (BM), and 3% cord blood units or multiple sources. Blood platelet counts and platelet transfusions were collected from 15 days pre-transplant until 100 days post-transplant. Platelet engraftment was defined as a platelet count ≥ 50 x10E3/mcL without a platelet transfusion in the previous 7 days. Pts (n=816) who achieved platelet engraftment and survived at least 30 days were selected for further analysis. Results: The 816 evaluable pts were divided into cohorts based upon their post-transplant survival: 146(18%) who died within 100 days post-transplant (early death); 267 (33%) that survived 100 days −2 years post-transplant (late death), 319 (39%) who survived > 2 years (long-term survival), and 84 (10%) were lost of follow-up within the first 2 years. Transfusion-independent platelet engraftment was achieved at median of 15 days post-transplant with no significant differences seen in the kinetics of initial engraftment among the different pt cohorts. Median platelet counts at different time points post-transplant were plotted for each pt cohort (Figure 1). Pts in the early-death cohort had a continuous decline in median platelet counts from engraftment values of > 50 x10E3/mcL to a median values of ∼20 x10E3/mcL. Univariate analyses indicated that higher platelet counts at day −15 (prior to conditioning) or at day 100 post-transplant were significantly associated with improved overall survival (HR of 0.63 and 0.39 respectively, P < 0.01). Cox-regression analysis was performed to evaluate significance of pre- and post-transplant platelet counts with clinical covariates that have been previously associated with survival including age, diagnosis, disease status and the source of the grafts. The multivariate model confirmed the significant association of the following factors with overall survival: higher platelet counts on day 15 pre-transplant (HR:0.81; 95%Cl:0.70∼0.93; P-value <0.01), the platelet count on day 100 post-transplant (HR: 0.62; 95%Cl:0.55∼0.70; P-value:<0.01 ), a diagnosis of acute leukemia (HR:1.64; 95%Cl:1.13∼2.39; P-value <0.01), a diagnosis of multiple myeloma (HR: 2.12; 95%Cl:1.05∼4.23; P-value= 0.04), a disease status of complete remission (CR) versus not in CR (HR: 0.66; 95%Cl:0.44∼0.97; P-value = 0.04), and age (HR: 1.01; 95%Cl:1.00∼1.02; P-value= 0.08). Kaplan-Meier estimates for survival were performed based upon stratification of pt groups on the platelet count at day-15 pre-transplant or the day +100 post-transplant platelet count (Figure 2). Pts with a platelet count > 80 × 10E3/mcL on day +100 had 5 year survival of more than 50% compared with 30% survival in the pt cohort with platelet counts < 50 x10E3/mcL on day +100. Conclusion: Pts with continuously low platelet count after initial platelet engraftment are at high risk for early death. Higher pre-transplant platelet may be a surrogate for disease status and extent of prior therapy and are associated with long-term survival among pts undergoing allogeneic HSCT. Post-transplant thrombopoiesis at day 100 is highly correlated with long-term survival after allogeneic HSCT, identifying a high-risk group of transplant pts for whom additional treatment strategies are needed. Disclosures: Gleason: Celgene, Merck, Millenium: Consultancy.

scholarly journals Bortezomib, Lenalidomide and Dexamethasone (VRD) Followed By Autologous Stem Cell Transplant for Newly Diagnosed Multiple Myeloma; The Mayo Clinic Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2147-2147
Author(s):  
M Hasib Sidiqi ◽  
Mohammed A Aljama ◽  
Angela Dispenzieri ◽  
Eli Muchtar ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Board Of Directors ◽  
Mayo Clinic ◽  
Research Funding ◽  
Advisory Committees ◽  
Post Transplant ◽  
Standard Risk

Abstract We retrospectively reviewed all patients receiving bortezomib, lenalidomide and dexamethasone induction followed by autologous stem cell transplantation (ASCT) within 12 months of diagnosis for multiple myeloma at the Mayo Clinic. 243 patients treated between January 2010 and April of 2017 were included in the study. Median age was 61 (interquartile range, 55-67) with 62% of patients being male. High risk cytogenetic abnormalities (HRA) were present in 34% of patients. 166 (68%) patients received some form of maintenance/other therapy post transplant (no maintenance (NM, n=77), lenalidomide maintenance (LM, n=108), bortezomib maintenance (BM, n=39) and other therapy (OT, n=19)). Overall response rate was 99% with complete response (CR) rate of 42% and 62% at day 100 and time of best response post transplant respectively. The four cohorts categorized by post transplant therapy were well matched for age, gender and ISS stage. HRA were more common amongst patients receiving bortezomib maintenance or other therapy post transplant (NM 18% vs LM 22% vs BM 68% vs OT 79%, p<0.0001). Two year and five year overall survival rates were 90% and 67% respectively with an estimated median overall survival (OS) and progression free survival (PFS) of 96 months and 28 months respectively for the whole cohort. OS was not significantly different when stratified by post-transplant therapy (Median OS 96 months for NM vs not reached for LM vs 62 months for BM vs not reached for OT, p=0.61), however post-transplant therapy was predictive of PFS (median PFS 23 months for NM vs 34 months for LM vs 28 months for BM vs 76 months for OT, p=0.01). High risk cytogenetics was associated with a worse OS but not PFS when compared to patients with standard risk (median OS: not reached for standard risk vs 60 months for HRA, p=0.0006; median PFS: 27 months for standard risk vs 22 months for HRA, p=0.70). In patients that did not receive maintenance therapy presence of HRA was a strong predictor of OS and PFS (median OS: not reached for standard risk vs 36 months for HRA, p<0.0001; median PFS: 24 months for standard risk vs 7 months for HRA, p<0.0001). Patients receiving maintenance therapy appeared to have a similar PFS and OS irrespective of cytogenetics (median OS: not reached for standard risk vs 62 months for HRA, p=0.14; median PFS: 35 months for standard risk vs 34 months for HRA, p=0.79).On multivariable analysis ISS stage III and achieving CR/stringent CR predicted PFS whilst the only independent predictors of OS were presence of HRA and achieving CR/stringent CR. The combination of bortezomib, lenalidomide and dexamethasone followed by ASCT is a highly effective regimen producing deep and durable responses in many patients. Maintenance therapy in this cohort may overcome the poor prognostic impact of high risk cytogenetic abnormalities. Table Table. Disclosures Dispenzieri: Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Lacy:Celgene: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Kapoor:Celgene: Research Funding; Takeda: Research Funding. Kumar:KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gertz:Abbvie: Consultancy; Apellis: Consultancy; annexon: Consultancy; Medscape: Consultancy; celgene: Consultancy; Prothena: Honoraria; spectrum: Consultancy, Honoraria; Amgen: Consultancy; janssen: Consultancy; Ionis: Honoraria; Teva: Consultancy; Alnylam: Honoraria; Research to Practice: Consultancy; Physicians Education Resource: Consultancy.

scholarly journals Autologous Hematopoietic Cell Transplantation in Patients with High Risk Multiple Myeloma: Post- Transplant Responses Do Not Translate to Longer Survival

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1979-1979
Author(s):  
Manish Sharma ◽  
Parmeswaran Hari ◽  
Jennifer Le-Rademacher ◽  
Amrita Krishnan ◽  
Yago Nieto ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Complete Response ◽  
Chromosome 1 ◽  
P Value ◽  
Stage At Diagnosis ◽  
Risk Markers ◽  
Advisory Committees ◽  
Post Transplant ◽  
African American Race

Abstract Background: Multiple myeloma remains an incurable disease with a heterogeneous clinical course, somewhat explained by the occurrence of high-risk prognostic markers. The International Myeloma Working Group defined high risk myeloma (HRM) as the presence of del17p13 or t(4;14) with ISS II/III. Conflicting data exist regarding t(14;16), hypodiploidy and chromosome 1 abnormalities (1q21 amplification, 1p deletion and others). Methods: We analyzed the outcomes of 142 HRM patients with high risk FISH or cytogenetic findings reported to the CIBMTR from 2008-2012 treated with an upfront (within 12 months of diagnosis), melphalan-conditioned autologous hematopoietic cell transplant and compared them to 573 patients with no high-risk markers (NHRM). Patients that received more than 2 induction regimens were excluded in this analysis. The HRM cohort comprised del17p13 (n=27), t(4;14) (n=27), t(14;16) (n=5), chromosome 1 abnormalities (n=42), hypodiploidy (n=13) and ≥2 high-risk markers (n=31). Planned post-transplant therapy was collected. Outcomes of interest included progression-free survival (PFS) and overall survival (OS). Results: The HRM and NHRM groups were similar to each other except for the following differences: HRM was associated with lower Karnofsky (KPS) (49% vs 36% with KPS<90, p 0.02) and higher stage at diagnosis (41% vs 28% with ISS/DSS III, p 0.008). More HRM patients received induction with bortezomib and immunomodulatory drug (imid) combinations (55% vs 43%, p <0.001) and had a lower complete response rate prior to transplant (12% vs 16%, p 0.04). More HRM patients had planned post-transplant combined bortezomib and imid therapy (27% vs 12%, p<0.0001). Median follow up in the 2 groups was 36 months for HRM and 44 months for NHRM. At 100 days post-transplant, similar numbers of patients had achieved complete and very good partial responses in the 2 groups (Table 1). At 3 years post-transplant, HRM patients had lower PFS (36% vs 50%, p <0.001) and OS (73% vs 85%, p <0.001) compared to NHRM. Univariate outcomes are shown in Table 2 divided by type of HRM. Table 3 shows the results of the multivariate analysis. The figure shows the Kaplan-Meier curves of probability of survival. Among the relapsed patients (HRM = 91, NHRM = 296), the 2 year survival was 48 (35-60)% for HRM and 70 (64-76)% for the NHRM groups, p-value 0.004. Conclusions: Patients with HRM achieved similar day 100 response compared to NHRM but were unable to maintain this response over time despite being more likely to receive post-transplant therapy. HRM was associated with shorter PFS and further shortened post-relapse survival. Patients with chromosome 1 abnormalities or del 17p alone appeared to have similar outcomes to those with NHRM while those with t(4;14) and those with more than 1 high-risk marker had the least favorable outcomes. In addition to HRM, obtaining less than complete response prior to transplant and the lack of post-transplant therapy were associated with worse PFS and OS. Finally, African-American race and higher stage at diagnosis were also associated with lower OS in our study. Table 1. Day 100 post-transplant response Variable HRM NHRM P-value Day 100 response 0.55 sCR/CR/nCR 40 (28) 176 (31) VGPR 43 (30) 174 (30) PR 39 (27) 129 (23) SD/NR 14 (10) 63 (11) Progression/relapse 5 (4) 13 (2) Missing 1 (<1) 18 (3) Table 2. Outcomes at 3 years post-transplant. Values are expressed as probabilities with 95% confidence intervals. NHRM t(4;14) del 17p Chr 1 ≥ 2 HR p-value PFS 50 (46-55)% 30 (12-51)% 44 (25-64)% 40 (24-56)% 23 (9-41)% <0.001 OS 85 (81-88)% 58 (36-78)% 81 (60-95)% 87 (74-96)% 65 (47-82)% <0.001 Table 3. Multivariate analysis Outcome Hazard ratio (95% CI) p-value PFS HRM vs NHRM 1.7 (1.3-2.3) <0.0001 Pre-transplant CR PR SD Progression 1 2.1 (1.2-3.7) 2.0 (0.8-5.0) 4.5 (1.9-10.3) 0.0245 0.008 0.14 0.0003 Planned post-transplant therapy vs no therapy 0.6 (0.4-0.8) <0.0001 OS HRM vs NHRM 2.0 (1.4-3.0) 0.0001 African-American race vs Caucasian 1.7 (1.1-2.5) 0.007 ISS/DSS III Yes vs No 1.8 (1.2-2.5) 0.0008 Pre-transplant CR PR SD Progression 1 1.4 (1.0-1.9) 1.8 (1.0-3.0) 2.7 (1.5-4.8) 0.008 0.03 0.02 0.0004 Planned post-transplant therapy vs no therapy 0.5 (0.3-0.8) 0.0001 Figure 1. Figure 1. Disclosures Krishnan: Onyx: Speakers Bureau; BMS: Consultancy; Janssen: Consultancy; Celgene: Consultancy, Speakers Bureau; Millenium: Speakers Bureau; Jazz: Consultancy. Gasparetto:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Honoraria; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Interest of Negative Minimal Residual Disease Estimated by Flow Cytofluorometry After Allogeneic Stem Cell Transplantation for B-Cell Chronic Lymphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2547-2547
Author(s):  
Caroline Algrin ◽  
Magali Le Garff-Tavernier ◽  
Oumedaly Reman ◽  
Vincent Levy ◽  
Anne Huynh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Advisory Committees ◽  
Flow Cytofluorometry ◽  
Post Transplant

Abstract Abstract 2547 Introduction. Minimal residual disease (MRD) eradication in patients with chronic lymphocytic leukemia (CLL) treated by standard chemo-immunotherapy regimens correlates with improved outcome. However, there is limited information about the interest of negative MRD after allogeneic stem cell transplantation (allo-SCT). In this study we investigated whether blood phenotypic remission could impact post-transplant outcome in patients with CLL. Methods. We retrospectively included patients who underwent allo-SCT for CLL and with post-transplant MRD monitored by four or six-colour flow cytofluorometry in blood samples (sensitivity≥10−4). Prognostic impact was evaluated on overall survival (OS) and progression-free survival (PFS). Each of these parameters was evaluated according to the best response and to the 12 month-MRD status, using log-rank test. Results. Thirty-three patients from 4 hematology departments were included. Median age at transplant was 54 years (range, 41 to 66 years). The median number of prior chemotherapy regimens was 3 (range, 1 to 6) including autologous stem cell transplantation in 48% of the patients. Status at transplant was available in 27 patients and 11% of them had negative MRD, 26% haematological complete response (CR), 59.% partial response (PR) and 4% had refractory disease. Twenty-two patients (67%) received a reduced intensity conditionning regimen. Conditioning regimen included serotherapy (antithymoglobulin n = 10, alemtuzumab n = 1, rituximab n = 1) in 12 patients. Twenty-two patients (67%) were transplanted with HLA identical sibling donor. The median number of MRD evaluations after transplant was 5 (range, 1 to 23). Response to transplant: After transplant, 16 patients achieved negative MRD, 15 patients achieved haematological CR, 1 PR and 1 did not respond to transplant. Among the 16 patients with phenotypic remission, negativation of MDR was obtained before the cessation of immunosuppressive therapy for 15 of them (94%) and median time to negativation was 7 months (range, 2 to 20 months). In patients achieving phenotypic remission chronic GVHD rate was 75% versus 44% in patients with post-transplant detectable MRD. Post-transplant outcomes: With a median follow-up of 27 months, the 2-y OS and the 2-y PFS were respectively 84% and 53%. Cause of death (n = 8) was progression in 4 cases and transplant related mortality in 4 cases. Impact of phenotypic remission: The achievement of phenotypic remission (whatever the time of evaluation) correlates with better PFS: 2-y PFS was 85% in these patients versus 27% in the other patients (p = 0.012). Considering the 19 patients with MRD evaluation available at 12 months after transplant, 2-y PFS was 100% in 12-month-negative-MRD patients (n = 10) versus 17% in positive-MRD patients at that date (p = 0.003) No relapse was observed in the group of patients who achieved phenotypic remission at 12 months post-transplant (figure). Conclusion. These data suggest that achievement of post transplant negative MRD in patients with CLL is associated with a long-term control of the disease and better PFS. In our series, no relapse occurred in patients with negative MRD at 12 months post transplant. These results could lead to decrease immunotherapy and to administrate donor lymphocytes to patients with post-transplant persistent positive MRD. Disclosures: Leblond: ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Addition of Rituximab Improves Outcome of HIV Negative Patients with Burkitt Lymphoma Treated with the Lmba Protocol: Results of the Randomized Intergroup (GRAALL-Lysa) LMBA02 Protocol. (IGR sponsored LMBA02, NCT00180882)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 685-685 ◽  
Author(s):  
Vincent Ribrag ◽  
Serge Koscielny ◽  
Krimo Bouabdallah ◽  
Gilles Salles ◽  
Olivier Casasnovas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
P Value ◽  
Intensive Chemotherapy ◽  
Advisory Committees ◽  
Extension Group ◽  
Disease Extension ◽  
Group B ◽  
Hiv Negative

Abstract Abstract 685 Background: Intensive chemotherapy is now considered as a standard of care in adult patients with Burkitt Lymphoma (BL). Although some single arm studies suggested that adding rituximab to these intensive short-course regimen could improve patientÕs outcome, no randomized study have been reported so far. Methods: To evaluate the potential benefit of adding rituximab to intensive chemotherapy, we conducted a phase III trial comparing the standard LMBA protocol (Divine et al, Ann Oncol 1995) to the same regimen plus rituximab. Rituximab (375 mg/m2) was given on day 1 and 6 during the first 2 courses of COPADM. Patient eligibility criteria included age >18 years, HIV negativity and previously untreated BL. The primary study objective was event-free survival (EFS). A study sample size of 250 pts was estimated in order to detect a 15% gain in EFS (two-side test, power 90%, type 1 error 5%). Secondary objectives were safety and overall survival. Treatment was adapted on disease extension (group B vs C) and age for patients from the C group (age <40; 40–59 and >59). Group C included patients with bone marrow and/or CNS involvement, and group B all the other patients. Methotrexate, cyclophosphamide and cytarabine doses were adapted to age in the group C. Lenograstim was given prophylactically to the pts. The randomization was stratified on disease extension (group B vs C) and age. Results: From October 2004 to September 2010, 257 patients from 45 centers were included; 128 in the Rituximab arm and 129 in the standard arm. Median age was 47 (26% were > 60), M/F ratio was 2.5, serum LDH level was > normal in 75% of the patients, and 11% had a performance status (PS)>2. The two treatment arms were well balanced for pretreatment characteristics, except for age and PS. Patients were older in the Rituximab arm (30%>60 years old vs 17% in the standard arm) or had a higher PS>2 (17% with PS>2 vs 7%). With a median follow-up of 38 months (range 0.3 to 79), patients treated in the rituximab arm had a better EFS (3 year EFS 76%; 95% CI: 69–84 vs 64% in standard arm; 95%CI: 55–72; Logrank P value stratified on treatment group=0.046), and Overall Survival (3 year OS 82%; 95% CI: 77–90 vs 71% in standard arm; 95%CI: 63–79; Logrank P value, stratified on treatment group=0.016) (Figure). Fifty-eight patients died. Causes of death were lymphoma (9 in the rituximab arm and 22 in the standard arm), toxicity (9 in the rituximab arm and 7 in the standard arm), and other causes (4 in the rituximab arm and 7 in the standard arm). Safety was similar in both arms for duration of grade 4 neutropenia, number of platelet or red cell transfusions, minor or major infection. Conclusions: The addition of rituximab to LMBA protocol improves EFS and OS in adult BL HIV negative. No adverse and/or increased toxicity was observed when rituximab was added to this intensive chemotherapy regimen. Toxic death rate was similar to our previous phase II experience despite a higher median age in this randomized multicenter trial. Disclosures: Ribrag: Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; Sanofi-Aventis: Research Funding; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Ruxolitinib is approved in the United States and Canada for the treatment of myelofibrosis and is being investigated in combination with panobinostat, an investigational product, in this indication. This abstract reports on a clinical trial conducted outside the US. All patients have provided written informed consent. Salles:roche: Membership on an entity's Board of Directors or advisory committees. Herbrecht:Pfizer: Advisory board member Other. Coiffier:roche: Membership on an entity's Board of Directors or advisory committees.

Further Evidence to Not Delay Transplant for Continued ARA-C Consolidation in Patients with Intermediate or High Risk AML

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5544-5544
Author(s):  
James K. Feisal ◽  
Nicholas B. Pleat ◽  
Michael Machiorlatti ◽  
Summer Frank ◽  
Sara Vesley ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Blood Cells ◽  
P Value ◽  
Myeloablative Conditioning ◽  
Risk Status ◽  
Post Transplant ◽  
Preparative Regimen ◽  
Reduced Intensity

Abstract Background: Allogeneic stem cell transplant (alloSCT) is indicated for patients with acute myeloid leukemia (AML) with high-risk disease on presentation or in relapsed or refractory cases. Durable elimination of leukemic burden after achieving a complete remission (CR) is thought to be an important prerequisite for successful transplant. Typically, this is achieved with consolidation treatments with cytarabine (ARA-C) in repeated cycles in non-refractory cases. Previous reports have suggested there is no apparent advantage for post-remission consolidation chemotherapy before reduced intensity transplant, provided a donor is readily available. Aim: To study the impact of the total cumulative dose of ARA-C in the pre-transplant setting before alloSCT either with reduced-intensity conditioning (RIC) or full myeloablative conditioning (MAC). Methods: We conducted a retrospective chart review at the University of Oklahoma and affiliated hospitals in patients with AML in complete remission from October 2006 to December 2014. Appropriate IRB approval was obtained in accordance with Helsinki declaration. Simple descriptive statistics were created for all covariates [mean, SD for continuous covariates and n (%) for categorical variables]. A Cox proportional hazards model was used to assess the association of each covariate with overall survival. Results: Sixty five patients were identified through our local leukemia registry with a mean age of 43, 57 (87.7%) were white, and 42 (64.6%) were male. Based on cytogenetics and molecular markers, 36 patients (55.3%) were intermediate risk and 20 patients (30.7%) were unfavorable risk status. For transplant preparative regimen, MAC was utilized in 50 cases (76.9%) and RIC was utilized in the other 15 (23.0%). Bone marrow stem cells were used in 28 cases (43.0%), peripheral blood cells were used in 26 cases (40.0%), and cord blood cells were used in the remaining 11 cases (16.9%). The mean dose of ARA-C given in consolidation was 43 g/m2 with standard deviation 31.5 g/m2. After adjusting for age and risk status, ARA-C consolidation was not associated with increased overall survival (OS) in the patients (p-value = 0.1776). When only considering those patients with myeloablative conditioning, ARA-C consolidation was still not associated with increased OS (p-value = 0.7533). Conclusions: Prior published data indicates that further ARA-C therapy given during consolidation does not correlate with improved outcomes post-transplant in patients with AML who received a reduced intensity preparative regimen. However, we attempted to expand this data to include patients who received a full myeloablative preparative regimen. Our experience using our single institution retrospective data suggests further ARA-C therapy given in consolidation does not benefit patients who underwent either RIC or MAC in terms of post-transplant survival. This provides further evidence that there should be no delay in moving patients to transplant, provided a suitable donor is available. Disclosures No relevant conflicts of interest to declare.

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