Pretransplatation PET as Major Prognostic Discriminant in IGEV (ifosfamide, gemcitabine, vinorelbine and prednisone) Treated Patients with Relapsed/Refractory Hodgkin's Lymphoma (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3707-3707
Author(s):  
Rita Mazza ◽  
Stefano Luminari ◽  
Massimo Magagnoli ◽  
Michele Spina ◽  
Teodoro Chisesi ◽  
...  
Keyword(s):  
Complete Remission ◽  
Fdg Pet ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Response To Therapy ◽  
High Dose ◽  
Bulky Disease ◽  
The Impact

Abstract Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Minimal Residual Disease (MRD) By Either Flow Cytometry or Cytogenetics Prior to an Allogeneic Hematopoietic Cell Transplant (allo-HCT) Predicts Poor Acute Myeloid Leukemia (AML) Outcomes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3221-3221
Author(s):  
Lakshmikanth Katragadda ◽  
Maxim Norkin ◽  
Myron Chang ◽  
Yunfeng Dai ◽  
Jan S Moreb ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Complete Remission ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Cox Proportional Hazards Model ◽  
Cell Transplant ◽  
Poor Risk ◽  
The Impact ◽  
Count Recovery

Abstract Introduction: Persistent AML is a known risk factor for poor outcomes after allo-HCT. The impact of MRD in patients who achieve complete remission (CR) or CR with incomplete count recovery (CRi) has been less well studied. Methods: We retrospectively reviewed the records of AML patients who underwent allo-HCT in morphological remission (<5% myeloblasts and normal marrow cellularity) with or without blood count recovery between January, 2000 and January, 2014. Data was collected for variables known to impact the prognosis of AML patients (Table 1). MRD was defined as evidence of abnormalities associated with AML by either flow cytometry, cytogenetics or Fluorescence in situ hybridization (FISH). The impact of MRD identified at the time of allo-HCT on cumulative incidence of relapse (CIR), progression free survival (PFS), and overall survival (OS) was assessed in MRD+ and MRD- patients. Results: A total of 166 eligible patients were identified. The median follow-up among living patients is 46 months (range, 13-103).Thirty seven (22%) patients had evidence of MRD (13 by flow cytometry only, 17 by cytogenetics/FISH only and 7 by both). MRD was more common in patients with poor risk karyotype at diagnosis and CRi at the time of allo-HCT (Table 1). PFS (P= 0.0016), OS (P=0.002), and CIR (P=0.02) were all significantly worse in MRD+ patients (Figures 1& 2). In univariate analysis, MRD+ patients, assessed by flow cytometry had worse PFS (P=0.0216) and OS (P=0.0314) compared to MRD- patients. Similarly patients with evidence of MRD+ by cytogenetics/FISH had worse PFS (P=0.007) and OS (P=0.0031). In a multivariate cox proportional hazards model 1) any MRD positivity prior to allo-HCT, 2) poor-risk karyotype at diagnosis, and 3) CRi at allo-HCT independently predicted significantly poor PFS and OS. Only poor-risk karyotype was associated with a significant increase in CIR, while MRD positivity showed a trend towards higher CIR. Conclusion: MRD positivity prior to HCT by either flow cytometry or by cytogenetics/FISH independently predicts adverse AML outcomes. Table 1. Comparison of pre-transplant variables Covariate Label MRD + (N=37) MRD - (N=129) P-Value Age(years) < 40 8 (21%) 20 (16%) 0.708 40 - 59 20 (53%) 69 (54%) ≥ 60 10 (26%) 39 (30%) Karyotype risk Favorable/ Intermediate 19 (53%) 95 (74%) 0.011 Poor 18 (47%) 33 (26%) Timing of Allo-HCT 1st remission (CR1) 28 (74%) 97 (76%) 0.792 > CR1 10 (26%) 31 (24%) Allo-HCT after1st relapse(>CR1): duration of CR1 > 12 mo 31 (82%) 113 (88%) 0.285 ≤ 12 mo 7 (18%) 15 (12%) Secondary AML No 23 (60%) 78 (61%) 0.964 Yes 15 (40%) 50 (39%) Complete remission vs CRi CR 28 (74%) 110 (86%) 0.077 CRi 10 (26%) 18 (14%) Conditioning Regimen Ablative 24 (63%) 72 (56%) 0.449 Other 14 (37%) 56 (44%) Donor Type Matched sibling donor 12 (32%) 42 (33%) 0.887 Other 26 (68%) 86 (67%) Female donor: male recipient (FDMR) Other 28 (80%) 91 (78%) 0.844 FDMR 7 (20%) 25 (22%) Disclosures No relevant conflicts of interest to declare.

Comparative Analysis of the Value of Consolidation with Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT) Versus High-Dose Cytarabine (HDAC) Based Chemotherapy in Patients (pts) with Acute Myeloid Leukemia (AML) with Chromosome Seven Abnormalities

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2029-2029
Author(s):  
Elias J. Jabbour ◽  
Hagop M. Kantarjian ◽  
Betul Oran ◽  
Farhad Ravandi ◽  
Hady Ghanem ◽  
...  
Keyword(s):  
Complete Remission ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Response To Therapy ◽  
Chromosome 7 ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
Hematopoietic Stem ◽  
Platelet Recovery

Abstract Abstract 2029 Background: The karyotype of leukemic cells in pts with AML is one of the most pronounced prognostic factors determining response to therapy and overall outcome. Pts with AML and chromosome 7 abnormalities have poor prognosis and AHSCT is highly indicated for such pts. Aims: To determine to what extent AHSCT reduces relapses and improve survival in pts with AML with chromosome 7 abnormalities compared with alternative post remission therapy. Methods: We reviewed 2167 consecutive pts with AML referred to our department between 2000 and 2011. Among them, 325 were diagnosed with chromosome 7 abnormalities as a single abnormality (n=53, 16%) or complex (n=272, 84%). Of these, 126 pts (39%) were induced with IA based regimen and 49 (39%) of them achieved a complete remission (CR) or complete remission without platelet recovery (CRp) and pursued consolidation therapy. These pts were matched with 33 pts with available donors who were referred to receive an ASHCT in first CR. Results: Median age for pts receiving consolidation chemotherapy versus AHSCT was 56 (range, 19–78) and 49 (range, 22–71) years, respectively (<0.001). Of the 33 pts who received an AHSCT, 17 received their stem cells from related siblings, 15 from unrelated matched donors, and 1 from a haplo-identical donor. Conditioning regimen were fludarabine and busulfan in 26 pts and fludarabine and melphalan in 7 pts. Graft versus host disease (GVHD) prohylaxis consisted mainly of tacrolimus and short methotrexate. Median time to engraftment was 12 days for neutrophils (range, 9–20) and 19 days for platelets (range, 10–53). Acute Grade 3/4 and chronic GVHD were observed at the rate of 3% and 45%, respectively. With a median follow-up of 29 weeks (range, 14–239) for pts receiving consolidation chemotherapy and of 168 weeks (range, 5–454) for pts receiving AHSCT, the 4-year event-free survival (EFS) rates were 4% and 51%, respectively (p<0.001). The median EFS for pts receiving consolidation chemotherapy and AHSCT were 17 (range, 1–330) and 51 (range, 1–456) weeks (Figure 1), respectively. The 4-year OS rates were 7% and 62%, respectively (p<0.001), with the median survival being 35 (range, 1–568) and 389 (range, 1–456) weeks, respectively (Figure 2). Conclusion: AHSCT applied as a consolidation in first CR in pts with chromosome 7 abnormalities is associated with a significant reduction of the relapse rate and improvement of OS compared to alternative post remission therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High-Dose Therapy and Autologous Hematopoietic Progenitor Cells Transplantation for Recurrent or Refractory Hodgkin's Lymphoma: Analysis of King Hussein Cancer Center Results and Prognostic Variables

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Fawzi Abdel-Rahman ◽  
Ayad Hussein ◽  
Mohammad Aljamily ◽  
Abdulhadi Al-Zaben ◽  
Nilly Hussein ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Hodgkin’S Lymphoma ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hodgkin's Lymphoma ◽  
Cancer Center ◽  
High Dose ◽  
The Impact

Purpose. to evaluate the outcome of patients with Hodgkin’s lymphoma who underwent autologous transplantation at KHCC bone marrow transplant program. Patients and Methods. Over 6 years, 63 patients with relapsed or refractory Hodgkin’s lymphoma underwent high dose chemotherapy followed by autologous transplant. There were 25.4% patients in complete remission (CR), 71.4% with chemotherapy responsive disease at the time of transplant. Prior to conditioning regimen, 56% received two chemotherapy lines, and, 44% received more than two lines. Results. The main outcomes of the study are the rate of complete remission at day 100, overall survival (OS), relapse-free survival (RFS), The impact of the following variables on OS and RFS: (a) disease status at the time of transplant, (b) number of chemotherapy lines prior to conditioning, (c) age group, (d) time of relapse < or >12 months were investigated. The CR at day 100 was 57%. The median overall survival for the whole group was 40.6 months; the median RFS was 20 months. The only factor which significantly impacts the study outcomes was the number of chemotherapy lines prior to conditioning on OS in favor of patients received two lines. Conclusion. In our study only the number of chemotherapy lines received before conditioning had statistically significant impact on OS.

scholarly journals Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1167-1167
Author(s):  
Andreas S. Buser ◽  
Laura Infanti ◽  
Andreas Holbro ◽  
Joerg Halter ◽  
Sabine Gerull ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Risk Scores ◽  
Employment Equity ◽  
Stem Cell Source ◽  
Equity Ownership ◽  
The Impact

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p <0.001, respectively). Primary disease status (p = 0.039); stem cell source (p <0.001); GVHD prophylaxis with ATG (p <0.001); total body irradiation (p <0.001); and conditioning regimen (p <0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p<0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p <0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Intensified CHOP (ICHOP) +/− Rituximab in Primary Mediastinal Diffuse Large B Cell Lymphoma (PMBCL): The Role of Doxorubicin/Cyclophosphamide Dose-Intensity

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3593-3593
Author(s):  
Rita Mazza ◽  
Monica Demarco ◽  
Michele Spina ◽  
Massimo Magagnoli ◽  
Luca Castagna ◽  
...  
Keyword(s):  
Complete Remission ◽  
Partial Remission ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Bulky Disease ◽  
Induction Failure ◽  
The Impact ◽  
Cyclophosphamide Dose

Abstract Background PMBCL is a clinical/biological distinct entity, sharing some characteristics with both classical DLBCL and Hodgkin’s lymphoma. MACOP B is considered the treatment of choice. Methods Starting from 1997, we treated PMBCL with an ICHOP regimen including cyclophosphamide 1750 mg/mq with MESNA uroprotection, doxorubicin 75 mg/mq, vincristine 1.4 mg/mq with 2 mg cap, and prednisone 100 mg d 1–5 of each 14-day courses, GCSF from day 7 to day 12. Rituximab (R) 375mg/mq/course was added to ICHOP (R-ICHOP) from 2002. Treatment plan included five courses of ICHOP±R. Cases with unfavourable prognosis according to age-adjusted International Prognostic Index (aaIPI2–3) were submitted to high dose chemotherapy (HDT) and peripheral stem cell rescue. Radiotherapy on involved sites was then delivered to all patients if at least partial remission (PR) was reached. Clinical response was evaluated through CT +/− Gallium scan (14 pts) up to 2002, and thorough CT + PET scan (16 pts) thereafter, according to Cheson criteria. Results: up to 2006, 30 pts were treated, with the following characteristics: M/F 10/20, median age 34 years (range 22–53), Ann Arbor stage I: 4, II –IIE:19, III: 1, IV: 6; bulky disease: 29; B symptoms: 14; aa IPI 0–1: 24, 2–3: 6; RICHOP/ICHOP 21/9. After ICHOP±R 15 patients achieved complete (CR) or unconfirmed complete remission (CRU), 14 PR, 1 stable disease. At the end of the whole program 29/30 pts reached CR and one progressed. Seven pts received HDT, six following ICHOP±R and one after II line chemotherapy for refractory disease. After a median observation time of 60 months 1 patient progressed and 1 patient relapsed, respectively. Both died of lymphoma. One patient with stage IIE IPI 0 relapsed 18 months after completion of ICHOP and RT and died after further 5 treatment lines including alloBMT. The other patient with stage II EB IPI 1, progressed shortly after R-ICHOP and RT and died five months later. Five-yr failure free survival and overall survival are 93.2 and 92.8, respectively. ICHOP±R was well tolerated, with neither toxic death or life-threatening toxicity. No patient interrupted the planned treatment because of toxicity. Hospitalization was required in seven cases due to febrile neutropenia (6), hemorrhagic cystitis (3 cases), and pneumonia (1). Five episodes of grade III–IV mucositis were observed in 4 patients. Of 147 delivered cycles, 25 were delayed (13 pts). Conclusion: in PMBCL, the results obtained with the ICHOP protocol are better than standard CHOP and comparable to MACOP-B, emphasizing the role of doxorubicin and cyclophosphamide dose-intensity. In this limited series, the impact of adding rituximab is not clear. R-ICHOP ICHOP Tot. Patients (N°) 21 9 30 * IPI 0; ^ IPI 1 IPI 0–1 16 8 24 IPI 2–3 5 1 6 Response to CT (N°) Complete Remission 10 5 15 Partial Remission 11 3 14 Induction Failure 0 1* 1* Response CT +RT+/− HDT (N°) Complete Remission 20 9 29 Partial Remission 0 0 0 Induction Failure 1 0 1 Relapse (N°) 0 1^ 1^ 5-yr FFP 95.2 88.9 93.2 5-yr OS 95.2 88.9 92.8 Median follow up (range) 52 months 104 months 60 months

Radioimmunotherapy (RIT) with 90yttrium Zevalin Followed by BEAM Conditioning Regimen (Z-BEAM) and Autologous Stem Cell Transplantation (ASCT) for the Treatment of High Risk Relapsed/Resistant Non Hodgkin's Lymphoma (NHL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3107-3107
Author(s):  
Barbara Botto ◽  
Chiara Ciochetto ◽  
Marilena Bellò ◽  
Roberto Passera ◽  
Giulia Benevolo ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Matched Pair ◽  
High Dose ◽  
Bulky Disease ◽  
Response Status

Abstract Abstract 3107 High dose chemotherapy (HDC) and ASCT is actually considered an effective treatment for relapsed NHL. Standard dose Zevalin (0.4 mCi/kg) combined with conventional BEAM (Z-BEAM) is a promising conditioning regimen for the treatment of high risk relapsed/resistant NHL. We evaluated the feasibility and the efficacy of Z-BEAM in a group of relapsed/refractory patients treated in a single institution. Between October 2006 and December 2010 twenty nine pts were treated with Zevalin (day –14) followed by standard dose BEAM (day –7 to –1) and ASCT. Patients were included into the study and considered at high risk of failure if showed: progression or early relapse (<1 year) from previous therapy or multiple relapses. Rituximab followed by standard dose DHAP or ICE were used as debulking and mobilizing schedule. Clinical characteristics were as follows: 14 refractory and 15 early or multiple relapse; 8 grade I-II follicular, 16 PML/DLBCL, 3 MCL, 2 indolent non follicular; 6 stage II and 23 stage III-IV; 10 patients had bulky disease and 15 bone marrow involvement; 9 LDH level above normal. 13 patients received only one previous line of treatment and 16 were treated with 2 or more lines before Z-BEAM, all containing Rituximab. Only 5/29 patinets received a reducted dose of 0.3 mCi/kg Zevalin because of low platelets counts. Response status before RIT was: 14 CR (49%), 9 PR (33%), 3 SD (9%) and 3 PD (9%). At the end of treatment response status is actually available in 26/29 pts: CR 18(69%), PR 5(19%) and PD 3 (12%). Overall response rate was converted from 81% before Z-BEAM and ASCT to 88% at the end of the entire program. Median CD34+ cells infused was 7.26 106/kilograms (range 4.43–8.9). All pts engrafted with median time to platelet and neuthrophils count higher than 20×109/l and 0.5×109/L of 11 and 10 days respectively. Febrile neutropenia occurred in 12/29 pts. One pulmonary Aspergillosis and 8 bacteriemia were documented. One patient experienced an intestinal perforation during aplasia and one cardiac failure was documented in a woman previously treated with cumulative antraciclines doses and mediastinal radiotherapy. With a median follow up of 15 months progression free survival (PFS) is 79% and overall survival is 83%. 4/14 pts before Z-BEAM showed a subsequent progression and 2/15 relapsed: five pts died of lymphoma. No toxic deaths were recorded. In this group of pts with high risk relapsed/resistant NHL Z-BEAM+ASCT is able to achieve a good response with engraftment and toxicity not different from standard BEAM. This approach needs to be tested in a larger multicenter study. A matched pair analysis to compare this group with a similar group treated with standard BEAM without Zevalin is actually planned in our institution Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Hematopoietic Recovery After Fludarabine, IV Busulfan and Antithymocyte Globulins (FB2 regimen) Reduced-Intensity Conditioning Regimen (RIC) Allogeneic Stem Cell Transplantation (allo-SCT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4483-4483
Author(s):  
Amandine Lebourgeois ◽  
Marion Loirat ◽  
Benoit Tessoulin ◽  
Elsa Lestang ◽  
Pierre Peterlin ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Prognostic Impact ◽  
Immune Recovery ◽  
Post Transplant ◽  
Factors Associated ◽  
Before And After ◽  
Circulating Lymphocytes ◽  
The Impact

Abstract Abstract 4483 Introduction: RIC regimens are increasingly used prior to allo-SCT. The FB2 regimen (Fludarabine 120–150 mg/m2 + IV Busulfan 6.4 mg/Kg + ATG Thymoglobuline 5mg/Kg) is currently the most widely used RIC regimen in many European centres. This retrospective analysis aimed to assess the hematopoietic and immune recovery in a homogeneously treated cohort of 53 patients (males: n=33; median age: 59 years (range: 22–70)) who received the FB2 regimen between January 2007 and October 2010 in our department. Patients and Methods: Diagnoses were as follow: AML n=23; ALL n=1; biphenotypic leukemia n=1; lymphoma n=16; myelodysplastic syndrome n=9; multiple myeloma n=3. Nineteen patients (36%) had received a prior autologous SCT. The majority of patients (n=40, 75.5%) were transplanted in complete remission. Thirty patients received a graft from a matched sibling donor (56.5%). All patients, but one (who received unmanipulated bone marrow) received G-CSF-mobilized PBSCs. GVHD prophylaxis consisted of cyclosporine (CsA) alone in patients transplanted with an HLA-identical sibling, and CsA+ mycophenolate mofetyl in other cases. None of the patients received G-CSF during aplasia following transplant while nine patients received erythropoietin before day+100. Results: Engraftment was achieved in 96% of patients (n=51). Median times for neutrophils (n=51) and platelets (n=22) recovery were 17 days (range: 0–39) and 10 days (range: 4–186), respectively. The majority of patients (n=31, 58%) did not receive platelet support during aplasia. The cumulative incidences of grade II-IV and grade III-IV acute GVHD were 30% and 15%, respectively, while overall incidence of chronic extensive GVHD was 33%. With a median follow-up of 19 months (range: 2–53), the 2-year OS, DFS, relapse incidence, and NRM were 63%, 59.5%, 35% and 6%, respectively. In univariate analysis, when regarding pre-transplant factors associated with outcome, the only factor correlated with a significantly higher 2-year OS and DFS was a higher total circulating lymphocytes count at transplant (> 730/mm3) (OS: 81.5% vs 43.2%, p=0.01; DFS: 73.2% vs 45.5%, p=0.03). Regarding post-transplant factors, we found that higher recovery of leukocytes (>5000/mm3) (2-year OS: 78% vs 46%, p=0.007; 2-year DFS: 70% vs 48%, p=0.08), neutrophils (>3230/mm3) (2-year OS: 76% vs 50%, p=0.02; 2-year DFS: 67.5% vs 52.0%, p=0.09), and monocytes (>590/mm3) (2-year OS: 80% vs 47%, p=0.004; 2-year DFS: 75% vs 42%, p=0.007) at day+30 post-transplant were the most significant factors associated with outcome. In multivariate analysis, the only independent factors associated with a significantly higher OS and DFS were a better immune status at transplant (lymphocytes count >730/mm3; HR 0.22; 95%CI: 0.08–0.63, p=0.005; and HR: 0.29; 95%CI: 0.12–0.71, p=0.006, respectively) and a higher monocytes count at day+30 post-transplant (>590/mm3) (HR: 0.24; 95%CI: 0.08–0.66, p=0.006; and HR: 0.28; 95%CI: 0.11– 0.68, p=0.005; respectively). Conclusion: These results suggest that hematopoietic status and recovery before and after FB2 RIC allo-SCT can be significant predictors of outcome. This paves the way for future studies aiming to closely monitor the kinetics of immune recovery after RIC allo-SCT and to evaluate the impact of growth factors and other immunostimulatory cytokines in the setting of RIC allo-SCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunophenotypic Response After Allografting In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3371-3371 ◽  
Author(s):  
Luisa Giaccone ◽  
Lucia Brunello ◽  
Roberto Passera ◽  
Moreno Festuccia ◽  
Milena Gilestro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
First Line ◽  
Significant Difference ◽  
The Impact

Abstract Background Minimal residual disease (MRD) by multiparameter flow-cytometry recently showed a promising role in predicting outcomes in patients with multiple myeloma. However, data on immunophenotypic response (IR) after allografting are lacking. Aim To evaluate the impact of IR and compare it to conventional complete remission (CR) following allografting in myeloma patients. Methods Sixty-six consecutive patients, median age 54 years (35-66), who underwent an allograft between January 2000 and December 2011 with a follow-up of at least 3 months were included. Disease response was evaluated by serum and urine electrophoresis, and bone marrow aspirate at baseline, 3, 6, 12, 18, 24 months after transplant and yearly thereafter. Skeletal survey or MRI were performed yearly or as clinically indicated (overt relapse or complaints of bone pain). Bone marrow aspirates had to contain at least 13000 cells/µL for flow-cytometry studies and IR was defined as absence of monoclonal plasma-cells detected by 4 or 6-colour staining with the following antibodies: CD38, CD138, CD56, CD19, CD45, cyKappa, cyLambda. CR was defined according to standard criteria (Durie et al, Leukemia 2006; 20:1467-73). Results Conditioning regimen was non-myeloablative 2Gy TBI-based in 55 patients, reduced intensity (fludarabine-melphalan-based) in 10 and myeloablative in 1 patient. Post-grafting immunosuppression consisted of cyclosporine with mycophenolate mofetil or methotrexate. Donors were HLA identical siblings in 58 patients and unrelated in 8. Only 1 patient received bone marrow as source of stem cells. Thirty-five/66 (53%) received the allograft as part of the first line treatment, whereas the remaining 31/66, (47%) were transplanted at relapse. At the time of transplant, 5/66 were both in IR and CR, 16 were only in IR and 4 patients were only in clinical CR. All 21 patients in IR at the time of transplant maintained it, while 26/45 (58%) entered IR after the allograft. Among patients surviving at least 3 months, overall treatment related mortality was 10.6% at 3 years. After a median follow-up of 69 months (range 19-147), the incidence of acute and chronic graft-versus-host disease was 45.6% and 49.3% without significant difference between responsive and non-responsive patients. At follow-up, overall, 24 patients achieved CR and IR (CR/IR group), 21 achieved IR but not CR because of persistence of urine/serum M-component (noCR/IR group), and 21 did not achieve either CR or IR (noCR/noIR group). Interestingly, none achieved CR without IR. Median overall survival (OS) and event-free survival (EFS) in patients who achieved IR were 96 and 55 months versus 36 and 7 months in those who did not (p<0.001). Median OS and EFS were not reached and 59 months in the CR/IR group, 77 and 15 months in the noCR/IR, and 30 and 5 months in the noCR/noIR respectively (p<0.001 for both EFS and OS-fig.1). In univariate analysis, being in the CR/IR group was the only significant predictor for prolonged OS and EFS (p<0.001). Of note, cumulative incidence of extra-medullary disease at first relapse after the allograft was 4% in the CR/IR, 32% in the noCR/IR and 15% in the noCR/noIR groups respectively (p<0.001). Receiving the allograft as first line therapy or later during the disease course did not significantly impact on OS and EFS. Conclusion The achievement of IR confers a favorable impact on OS and EFS after allografting. A higher incidence of extra-medullary in the noCR/IR group (some 30% of our patient cohort) may suggest that myeloma cells escape immune control outside the bone marrow. In this group, imaging studies such as positron emission tomography may clinically be indicated during follow-up to detect early relapse. Disclosures: No relevant conflicts of interest to declare.

Autografting Followed Closely by Nonmyeloablative Allografting as Consolidation Immunotherapy Reduces Disease Progression Compared to Tandem Autografting in Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1126-1126
Author(s):  
A.M. Carella ◽  
M. Spriano ◽  
M. T. Corsetti ◽  
P. Scalzulli ◽  
G. Beltrami ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Disease Progression ◽  
Remission Rate ◽  
Conditioning Regimen ◽  
Clinical Signs ◽  
Disease Free Survival ◽  
Disease Status ◽  
High Dose ◽  
Immunological Responses

Abstract Autografting (AutoSCT) has been limited by high-relapse rates and conventional allografting (AlloSCT) by excessive TRM and toxicity in the treatment of Multiple Myeloma (MM). Reduced intensity conditioning for transplant (RICT), a less toxic procedure for AlloSCT that aims to exploit graft versus tumor effect, has been shown to achieve remissions in MM. High-dose therapy/AutoSCT followed shortly thereafter by RICT might improve outcomes in MM as compared to AutoSCT or conventional AlloSCT used alone. We compared two retrospective cohort of patients who underwent either tandem AutoSCT (HDT consisted of Melphalan 200 mg/m2) or AutoSCT followed closely by related RICT (patients with HLA-matched siblings). The two groups were matched for pre-transplant therapy, disease status at transplant, time from diagnosis to transplant. GVHD prophylaxis for RICT patients consisted of CyA/MTX. The major results are summarized in the Table. In the AutoSCT/RICT group the complete remission rate was higher (p=0.004) and the risk of disease progression after transplant was significantly reduced (p=0.005). All patients who reached CR responded after full chimerism and GVHD developed. This finding confirms the existence of a graft-versus-myeloma effect. Since the first clinical signs of response in remitters patients were noted between 70 and 120 days and maximum response between 160 and 200 days after RICT (after DLI in one patient), these responses should be considered immunological responses. These data suggest than an allograft following an AutoSCT significantly reduces the incidence of disease progression. Tandem ASCT (N=35) ASCT + RICT (n=20) Age, median 56 (range, 38–66) 51 (range, 34–63) Median prior cycles of Chemoth. 4 (range, 3–6) 4 (range, 3–6) Time from Dx to 1st AutoSCT (median mo.) 6 (range, 5–60) 9 (range, 7–42) Conditioning Regimen for AutoSCT Melphalan (200 mg/m2) Melphalan (200 mg/m2) Conditioning Regimen for RICT --- TBI/Fludarabine Complete Remission 14% 50% p=0.004) Disease-Free Survival at 3 yrs 11% 45% (p=0.005) Overall Survival at 3 yrs 66% 70% (p=NS) Median Follow-Up (mo.) 30 (range, 6–104) 38 (range, 5–59) Transplant-Related Mortality 0% 0% Median days from AutoSCT to RICT --- 80

The Influence of PET/Gallium (PET/Gal) Status and High-Dose Rituximab (HDR) in Patients with Aggressive, Large, B-Cell Lymphoma (LBCL) Receiving Autologous Stem Cell Transplants (ASCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3058-3058 ◽  
Author(s):  
Amin M. Alousi ◽  
Rima M. Saliba ◽  
Grace-Julia Okoroji ◽  
Chitra Hosing ◽  
Barry I. Samuels ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
De Novo ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Disease Status ◽  
High Dose ◽  
Free Survival ◽  
The Impact

Abstract Background: PET/Gal status has been reported to be an important predictor of outcome in patients with LBCL who receive an ASCT. Newer conditioning regimens which include high-dose rituximab (HDR) have been shown to improve results (Khouri, JCO, 2005). The impact of HDR on the outcome of patients based on PET/Gal status has not been determined. Methods: A retrospective review of patients with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and PET/Gal status. In patients who received HDR, it was given with stem cell mobilization and then again on days +1 and +8 following transplant. Results: A total of 188 patients were identified. Median age was 49 years with 108 (57%) male patients. 147 patients (78%) had de novo LBCL and 41 (22%) had a LBCL of follicular origin (LBCL-F). 83 (39%) patients received HDR. At transplantation, 95 patients (50%) were in PR, 71 (38%) in CRU and 22 (12%) in CR. 142 (76%) patients were PET/Gal negative, 37 (20%) PET/Gal positive and 9 (4%) were unknown. Median follow-up was 47 months. On multivariate analysis, for patients with de novo LBCL, PET/Gal status and HDR were the only predictors for progression and progression free survival (PFS). Patients who were PET/Gal negative and those that received HDR had a hazard ratio (HR) of 0.3 (p<0.001) and 0.5 (p=0.02) for progression, respectively (see the table below for the cumulative incidence (CI) for progression and PFS at 54 months according to HDR and PET/Gal status for de novo LBCL undergoing ASCT). PET/Gal Status and HDR were also found to be predictive for patients with LBCL- F on univariate analysis, however due to the small numbers in this subset; multivariate analysis could not be performed. PFS at 54 months for patients with LBCL-F who were PET/Gal negative was 40% versus 17% in the PET/Gal positive group, (p=0.006). PFS for those LBCL-F patients who received HDR was 81% as compared to 23% for those who did not receive HDR, (p=0.007). Conclusions: The two most important predictors of outcome following ASCT are PET/Gal status and whether HDR was given with the transplant regimen. The addition of HDR to the transplant regimen decreases the risk for progression irrespective of PET/Gal status; however the improvement is more significant in patients with a negative PET/Gal scan. C.I. for progression and PFS at 54 months for de novo DLBCL PET/Gal Status HDR CI of Progression (%) Progression Free Survival Positive No 83 17 Positive Yes 54 45 Negative No 35 55 Negative Yes 22 75

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