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.

High Dose Sequential (HDS) Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Salvage Treatment of Hodgkin’s Disease (HD): A Brazilian Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5103-5103
Author(s):  
Bruno K.L. Duarte ◽  
I.S. Valente ◽  
Afonso C. Vigorito ◽  
Francisco J.P. Aranha ◽  
Gislaine B. Oliveira ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Gvhd ◽  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
High Dose ◽  
Bulky Disease ◽  
Hematopoietic Stem ◽  
Free Survival

Abstract From May 1998 to November 2006, 77 HD patients who used the regimen of high dose cyclophosphamide HD (CY) 7 or 4g/m2, methotretaxe 8g/m2 and etoposide 2g/m2 followed by AHSCT were analyzed. Their median age was 25.8 (8.8–71.5) years, 46 males and 31 females. At diagnosis 50 (65%) were stage III or IV disease, 10 (13%) had bone marrow involvement, 29 (37.7%) bulky disease and 55 (71.4%) B symptoms. Besides that, all patients were submitted to a mean of 2 (1–4) chemotherapy lives and their status were 3 (3.9%) complete remission (CR), 17 (22.1%) partial remission (PR), 57 (74%) progression disease (PD) or in non-specified sensitivity relapse. Concerning CY dose 30 (39%) received 4 g/m2 and 47 (61%) received 7 g/m2. After the HDCY 16 (20.8%) were in CR, 22 (28.6%) PR, 28 (36.3%) remained in DP and 11 (14.3%) died most in PD. After a median follow-up of 3.97 (1.13–55.9) months, 53 (68.8%) patients were submitted to AHSCT and their present status is 30 alive [18 CR, 2PR and 10 DP]; 23 dead [2 CR, 14PD and 7 related to the procedure]. Overall survival for transplanted patients was 55% in 8 years. Currently we have 33/77 (43%) alive patients, 19 CR, 3 PR, 11 PD. Overall Survival (OS) for whole group was 32%, Disease Free Survival (DFS) 64% and Progression Free Survival (PFS) 40%. Patients who were in DP or relapse prior to the HDCY (57) compared to their status after that had a significant improvement (P=0,001), their OS was 40% to CR-PR group (24) versus 16% PD group (33). In general, mortality was 44 (57%), their cause was 19 PD (43.2%), 8 (18.2%) related to HDCY, 2 (4.5%) related to HDMTX, 7 (16%) related to AHSCT, 6 (13.6%) infections, 1 (2.3%) chronic GVHD after a reduced intensity conditioning regimen transplant and 1 (2.2%) AML. Besides that, 3 patients developed MDS and 1 developed AML. In conclusion, although it had happened a significant number of toxicity related deaths, the sequence is feasible, mainly for sensitive patients and presents an acceptable response. The authors emphasize the high frequency of poor prognosis patients and occurrence of MDS/AML in 4 (5.2%) patients.

The Utility of Consolidative Upfront High Dose Chemoradiotherapy and ASCT in Patients with Mantle Cell Lymphoma (MCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2072-2072
Author(s):  
Daniel Persky ◽  
Carol S. Portlock ◽  
Simone Lessac-Chenen ◽  
Alexia Iasonos ◽  
Andrew D. Zelenetz ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Significant Difference ◽  
Dose Dense

Abstract Introduction: Two approaches to improve progression-free survival (PFS) in MCL are intensifying induction, as with hyperCVAD/M-A regimen, or intensifying consolidation with high dose chemoradiotherapy (HDT) and ASCT as in the prospective European MCL Network Trial. At MSKCC the strategy is to incorporate both approaches by administering an anthracycline-containing regimen in a dose dense fashion (CHOP- or R-CHOP-14) followed by consolidation with ICE (ifosfamide, carboplatin, etoposide) and HDT/ASCT. Patients: Forty six patients with newly diagnosed MCL underwent HDT/ASCT between 11/96 and 2/05. The median age was 55 years; 74% were male; 72% had bone marrow involvement, 39% had GI involvement, 7% were in leukemic phase, and 91% presented with stage IV disease. Splenomegaly was seen in 35%, B symptoms in 9%, KPS>70 in 93%, elevated LDH in 23%, and blastoid histology in 9%. Results: Induction was 4 to 6 cycles of CHOP-14 (43%), R-CHOP-14 (37%), or other doxorubicin-containing regimen (20%). Consolidation was performed with 2–3 cycles of ICE in 53% or R-ICE in 39%. Upfront treatment was well tolerated and permitted adequate stem cell collection and prompt transition to HDT/ASCT. Conditioning regimens were TBI/CY/VP-16 (59%) and BEAM (41%). Involved field radiation therapy was administered to 65%. Post-ASCT rituximab maintenance was given to 39%, with 57% of patients receiving rituximab as part of their treatment. Anthracycline-based induction led to CRu of 44% and ORR of 98%. Seventy two percent of patients were transplanted in CR, while the remaining 28% were in PR. At a median follow-up of 2.5 years (range 0.4–8.0 years) 17% of the patients have died and 24% have had progressive disease. The median OS and PFS have not been reached (lower 95% CI, 5.7 years and 4.4 years, respectively). The 5-year PFS and OS are 58% and 83%, respectively. The use of rituximab at any point during treatment prolonged PFS - only 1 of 26 patients receiving rituximab relapsed, as compared to 10 of 20 patients who were rituximab naive (p=0.03); thus far there is no significant difference in OS. There was no day 100 treatment related mortality. One patient developed bronchiolitis obliterans after ASCT and died of pulmonary fibrosis 6.5 years later; 3 patients have died of secondary cancers - one case each of MDS (1.6 years after ASCT), melanoma and lung cancer. Conclusion: These data provide evidence that dose-dense induction with CHOP-14 or R-CHOP-14 and consolidation with ICE/HDT/ASCT appears to be safe and effective, with minimal acute toxicity. Although the median follow-up is short, the use of rituximab appears to improve PFS. This contrasts with the findings of German LGLSG and may be a consequence of in vivo rituximab purging. Future therapy could incorporate all the successful elements of prior treatment programs, including R-CHOP-14, R-ICE, and radioimmunotherapy with high dose chemotherapy conditioning regimen, followed by ASCT and rituximab-based maintenance. PFS stratified by Rituximab PFS stratified by Rituximab

Pre-Transplant Ganciclovir and High-Dose Valacyclovir Prophylaxis Decrease Incidence of CMV Reactivation In High-Risk Seropositive UCBT Recipients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 678-678
Author(s):  
Filippo Milano ◽  
Steven Pergam ◽  
Hu Xie ◽  
Jonathan Gutman ◽  
Ivy Riffkin ◽  
...  
Keyword(s):  
High Risk ◽  
Proportional Hazards Model ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Cox Proportional Hazards Model ◽  
Prevention Strategy ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract Abstract 678 Background: Umbilical cord blood transplant (UCBT) recipients are high risk for cytomegalovirus (CMV) complications due to delayed and insufficient immune reconstitution. Since CMV viral load has been shown to be associated with the development of disease, an intensified prevention strategy was adopted at the FHCRC (Seattle, WA) which consists of pre-transplant ganciclovir (from day -8 to day -2), and high-dose acyclovir ([HDA] 2 gm valacyclovir 3 times daily) with preemptive bi-weekly monitoring for CMV DNA in serum from day 0 until day +100. Methods: We set out to compare rates of CMV reactivation and disease through day +100 in high-risk CMV seropositive UCBT recipients who received either the intensified strategy (G+HDA) or standard dose of acyclovir/valacyclovir (SDA, acyclovir 800 mg or valacyclovir 500 mg twice daily). All patients underwent weekly plasma testing for CMV by polymerase chain reaction (PCR). Our primary outcomes of interest were any CMV reactivation or disease by day 100. Risk factors for CMV reactivation were assessed using a multivariate Cox proportional hazards model. Results: Of the 105 UCBT recipients transplanted at the FHCRC between 1/2006 and 12/2009, 61 (58%) were CMV seropositive and eligible for inclusion in the cohort. In total, 31/61 (51%) received SDA and 30 (49%) G+HDA. The median patient age was lower in the SDA group 21.3 (interquartile range [IQR] 14.8–46.7) years and 30.1 (IQR 10.1–41.8) for G+HDA group, but other demographic factors were similar. Overall, the cumulative incidence of CMV reactivation was significantly lower in the G+HDA group (60% vs. 96.7; p=0.001 [Gray's test]) (Figure 1). In patients receiving G+HDA, the median time to first positive CMV PCR occurred later (27 days [IQR 11–35]) when compared to those given SDA prophylaxis (17 days [IQR 8–25]) (p=0.26). Additionally, the G+HDA group had significantly lower initial (71 copies/mL [IQR 47–110] vs. 235 [IQR 63–760], p=0.006) and maximum PCR viral loads (VL) (170 copies/ml [IQR 88–310] vs. 3200 [1400-11000], p<0.001) when compared to those receiving SDA prophylaxis. In multivariate analyses, the G+HDA prophylactic strategy was also associated with a significant reduction in CMV reactivation (HR 0.31; 95% CI 0.16–0.58; p<0.001). Over the first 100 days following transplant, there were fewer episodes of invasive CMV disease in the G+HDA group (1/30, 3% [1 pneumonia]) than under SDA prophylaxis (5/31, 16% [1 disseminated, 2 pneumonia, and 2 GI]) (p=0.09). In the SDA group 2/5 (40%) patients died secondary to CMV disease, and an additional 2 patients developed fatal CMV pneumonia after day 100 (day 165 & 191); no CMV related death or cases of late disease developed in the group receiving G+HDA prophylaxis. There was no evidence of increased toxicity by either median and maximum creatinine levels or days to engraftment when comparing the two regimens. Conclusions: Our study demonstrates that G+HDA was effective in preventing CMV complications in UCBT recipients. This intensified prevention strategy was associated with a decreased rate of CMV reactivation and appeared to significantly alter CMV replication dynamics. Importantly, the increased valacyclovir exposure did not alter the risk for developing either renal or hematologic toxicity. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Defibrotide for Prophylaxis of Hepatic Veno-Occlusive Disease in Autologous, Non-Purged Peripheral Stem Cell Transplantation for High Risk Neuroblastoma Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5910-5910
Author(s):  
Emel Unal ◽  
Nurdan Tacyildiz ◽  
Gulsan Yavuz ◽  
Handan Dincaslan ◽  
Gulsah Tanyildiz ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Occlusive Disease ◽  
High Dose ◽  
Peripheral Stem Cell ◽  
Peripheral Stem Cell Transplantation

Abstract High-dose chemotherapy (HDC) represents the standard of treatment for high-risk neuroblastoma(NBL), hepatic veno-occlusive disease (VOD) is a common, 10-50% and serious complication of haematological stem cell transplantation (HSCT), with up to 90% mortality rates. We planned study to assess whether the use of prophylactic defibrotide in paediatric patients who were heavily treated with chemo-radiotherapy before transplant, and then underwent autologous HSCT. Seventeen patients who underwent autologous, unpurged peripheral stem cell transplantation PBSC with a high risk of developing VOD, between January 2003-July 2014, were given Defibrotide prophylaxis 25mg/kg/day for 30 days, commencing on -1 of conditioning regimen. All patients were stratified by INSS stage, age, N-MYC status. All were treated with six cycles of induction chemotherapy, myeloablative intensification, surgery for primary site, radiation therapy to the primary tumour site plus metastatic sites i.e bone metastases including skull. Meta-iodobenzylguanidin treatment as targeted radiotherapy was given on -21 prior to myeloablative chemotherapy. Oral 13-cis retinoic acid was employed on day +90 post-transplant. CD34+ cell mobilization and PBSC collection was carreid out after two-four cycles of induction cycles. Conditioning regimen and stem cell infusion was done following four-six weeks of last chemotherapy cycle, in order to reduce the toxicitiy. Conditioning regimen CEM consisted Carboplatin, Etoposide, Melfalan. There were no toxic deaths. All of the patients receieved antimicrobial prophylaxis and total parenteral nutrition support when was needed. Myeloid engraftment on day+13, erythroid engraftment on day+18 and thrombocyte engraftment was achieved on day +23. Defibrotide prophylaxis seems to reduce incidence of VOD and is well tolerated. VOD incidence and severity was reduced in the defibrotide group which suggests that defibrotide might be effective in preventing and treating VOD. Sufficiently powered randomised trials are now required to definitively test the role of defibrotide in this setting. Disclosures No relevant conflicts of interest to declare.

Haploidentical Transplantation (HAPLO) with Post-Transplant High-Dose Cyclophosphamide for Graft Vs Host Disease (GVHD) Prevention in the Treatment of High Risk Hematological Neoplasms

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4545-4545
Author(s):  
Jorge Gayoso ◽  
Mi Kwon ◽  
David Serrano ◽  
Pascual Balsalobre ◽  
Javier Anguita ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Haploidentical Transplantation ◽  
Gvhd Prophylaxis

Abstract Abstract 4545 Introduction: Allogeneic transplantation is the only curative option in the treatment of multiple high risk hematologic neoplasms. Only 25–30% of patients have an HLA identical sibling donor and searching for a compatible unrelated donor or cord blood renders satisfactory results in around 60–70%. Haploidentical transplantation (HAPLO) offers a therapeutic alternative to more than 95% of such patients with the advantages of quick availability, easy programming and a committed donor. Patients and Methods: We evaluate the results of HAPLO with a reduced intensity conditioning regimen (Fludarabine 30 mg/m2 ×5 days (-6 to -2), Cyclophosphamide 14,5 mg/kg ×2 days (-6 and -5), IV Busulfan 3,2 mg/kg × 1–3 days (BUX, days -4 to -2) employing high doses of Cyclophosphamide post graft infussion (50 mg/kg days +3 and +4) as GVHD prophylaxis together with standard doses of cyclosporine and mycophenolate from day +5. Results: From Dec-2007, we have done 26 HAPLO in 4 spanish centers. Median age was 38 years (16–57), 20 were male and all were in advanced phases of their diseases (12 Hodgkin′s, 6 AML, 3 ALL, 2 MM, 1 MDS, 1 MF y 1 NHL). Previous autologous HSCT has been employed in 13 and allogeneic HSCT in 6 (2 MURD and 4 UCB). Disease status at HAPLO was CR in 8, PR in 14 and refractory in 4. Bone marrow was used in 16 and unmodified peripheral blood in 10. The haploidentical donor was patient′s mother (8), father (3), siblings (11) or other relatives (4). BUX was used in 1 dose (15), 2 doses (8) or 3 doses (2) and TBI 200 cGy in 1 case. Mean neutrophils engraftment was achieved on day +18 (13–26) and platelets >50K on day +27 (17–150) in all but 2 cases of graft failure (7.7%) due to progression (MF) or relapse (M7-AML). Main toxicities were grade 1–2 mucositis in 50%, febrile neutropenia in 75% and CMV reactivations in 58% with a 100 days NRM of 3.8% (1/26, VOD and MOF) and 10% NRM at 6 months (2/20). Grade II-IV acute GVHD appeared in 10/23 patients at risk (43%) and grade III-IV in 4/23 (17%). Chronic GVHD affected to 4/15 (27%), being extensive in 1/15 (6.7%). With a median follow-up of 9 months (1–38), 13/22 (59%) are alive in CR, progression or relapse has ocurred in 6/24 (25%). Immune reconstitution seems fast and complete in those evaluated. Conclusions: HAPLO with high-dose cyclophosphamide as GVHD prophylaxis is a useful alternative in the treatment of high risk hematologic tumours, with low toxicity, acceptable GVHD incidence and severity, long lasting remissions, and fast immunological reconstitution. Disclosures: No relevant conflicts of interest to declare.

The Addition of Rituximab to CVP (Bagley) + Interferon-α as Induction Regimen, Significantly Increases Complete Remission Rates and Progression Free Survival In Intermediate-High Risk Follicular Lymphoma Patients (LNH-pro vs. LNH-pro-05 trial)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2867-2867
Author(s):  
Jimena Cannata-Ortiz ◽  
Concepción Nicolás ◽  
Ana García-Noblejas ◽  
Javier Lopez ◽  
Maria José Requena ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Remission Rates ◽  
Induction Regimen

Abstract Abstract 2867 Introduction. Survival of Follicular Lymphoma patients has significantly increased with the introduction of immunomodulatory agents, such as Interferon (IFN) and Rituximab (R). Until 2002 our Follicular Lymphoma patients were included in a trial and received induction therapy with CVP + Interferon (LNH-pro, JCO 16; 1538–1546). Since 2006, Rituximab is being added to the same induction regimen (LNH-pro-05, EHA 09). Herein we communicate the comparative results between these two trials in Intermediate-High risk Follicular Lymphoma patients. Aim. To compare toxicity and efficacy in terms of complete remission (CR) and Progression Free Survival (PFS) between both trials in Intermediate-High risk Follicular Lymphoma patients. Methods. Patients in the LNH-pro trial (1990-2006) received CVP (CY 400mg/m2 p.o D1-5, VCR 1.4mg/m2 iv D1, PRD 100mg/m2 po D1-5) + IFN (3MU/m2 sc, 3 times/wk, for 12 wks). When it became available, G-CSF support was permited. In the LNH-pro-05 trial (2006-ongoing), Rituximab (R: 375mg/m2 iv D1) was added to the same induction regimen. All patients received 8 cycles as per protocol, with G-CSF support and Pn. jiroveci prophilaxis. In both studies, complete re-assessment was performed after cycle 4, at the end of induction therapy, every 4 months for the first 2 years and every 6 months thereafter. Results. We analysed data from 74 and 36 FL patients with FLIPI≥2, included in the LNH-pro and LNH-pro-05 trials, respectively. Patients' characteristics are shown in table 1. No significant differences were found between groups, except for a higher incidence of elevated B2-microglobulin in patients treated with CVP+IFN and higher Bulky disease (>7cm) among patients with R+CVP+IFN. Median number number of cycles were 6 and 8, respectively. Response: Seventy one patients (96%) in the LNH-pro Trial (CVP+IFN) were evaluable for response. Overall Response (OR) rate was 87%, with 68% Complete Remission (CR) and 19% Partial Remission (PR) (9% non-responders). In the LNH-pro-05 Trial (R+CVP+IFN), 36 patients (92%) and 33 patients (83%) were evaluable for response after 4th and 8th cycle. At cycle 4, all assesed patients achieved remission (15% PRs and 85% CR+uCR), while after the 8th cycle 100% of patients are in CR or uCR. Toxicity. Main hematologic grade 3–4 toxicity was neutropenia, 33% for CVP+IFN and 28% for R+CVP+IFN, with 12% and 6% of infections, respectively. Other non-hematologic toxicities were infrequent and mild (5% and 10% in each group). Eight percent of patients in the LNH-pro trial withdrew treatment due to toxicity. At the moment, none of the patients in the LNH-pro-05 trial have experienced an unacceptable toxicity. Survival . Median follow-up was 7.7 years for CVP+IFN and 2 years for R+CVP+IFN. A significant increase of PFS was seen among patients who received R (66% vs. 86%, at 3 years, P 0.05). There is also a trend to a longer overall survival in patients treated with R+CVP+IFN (P 0.07). Conclusion. The addition of Rituximab to CVP+IFN induction regimen in Intermediate-High risk Follicular Lympoma patients, significantly increases complete remission rates (88% to 100%) and progression free survival (86%, at 3 years), with a low toxicity profile. Disclosure: No relevant conflicts of interest to declare.

Autologous (Auto) Peripheral Blood Stem Cell (SCT) As a Consolidation Therapy for Patients with Acute Myeloid Leukemia (AML) in 1st Complete Remission (CR): A Single Institution Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4505-4505
Author(s):  
Amanpreet Buttar ◽  
Deepa Jagadeesh ◽  
Jan Cerny ◽  
Muthalagu Ramanathan ◽  
Zheng Zhou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Medical Center ◽  
Progression Free Survival ◽  
High Dose ◽  
Consolidation Therapy ◽  
Platelet Recovery ◽  
Entire Cohort

Abstract Abstract 4505 Introduction: Patients with AML in 1st CR are frequently consolidated with an auto SCT but the role of this modality in the management of AML is still not fully defined. Methods: Retrospective analysis was performed on all patients who underwent an auto SCT for AML in 1st CR at UMass Memorial Medical Center from January 2000 to December 2010. Data was analyzed as of August 2011. The study was approved by UMass Memorial Medical Center IRB. Results: 25 Patients were identified from the database. There were 13 males and 12 females. The median age was 46 years range (19–72). Cytogenetics was good risk in 6 patients, intermediate risk in 14, poor risk in 3 and unknown in 2 patients. Induction chemotherapy was standard dose Ara-C based in 13 patients and high dose Ara-C based regimen in 12 patients. Median time from diagnosis to transplant was 133 days range (107–362). Stem cell mobilization regimen consisted of Ara-C/Etoposide (E) in 21 (80%), Cyclophosphamide (Cy) in 3 (12%) and Mitoxantrone/Ara-C/E in 1 (4%). Preparative regimen included Busulfan (Bu) 4/ E in 17 (68%), Bu4/Cy in 5 (20%) and high dose Melphalan in 3 (12%). A median of 4.56 ×106 range (1.05 × 106 – 9.67 × 106 ) CD34 cells/kg were infused. 3 patients failed to engraft. Median time to neutrophil recovery was 11 days range (9 to 16) and platelet recovery was 20 days range (9 to 116). 100 day mortality was 12% (3/25). Median follow of the entire cohort is 6.5 years range (0.6 – 10.7). Total of 9 patients died. The cause of death included disease in 7, sepsis in 1 and unknown in 1 patient. Kaplan Meier estimate for progression free survival (PFS) and overall survival (OS) was 72% and 80% at 6 months and 62% and 61% at 3 years. Conclusion: ASCT is an effective and safe intensive consolidation therapy for patients with AML in 1st CR. Disclosures: No relevant conflicts of interest to declare.

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.

Comparative Analysis of Autologous Hematopoietic Cell Transplantation with Radioimmunotherapy (RIT) Based Conditioning Versus Total Body Irradiation (TBI) for High-Risk Diffuse Large Cell Lymphoma (DLCL): Toxicity and Efficacy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 32-32 ◽  
Author(s):  
Amrita Krishnan ◽  
Joycelynne Palmer ◽  
Auayporn Nademanee ◽  
Andrew Raubitschek ◽  
Dave Yamauchi ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Large Cell ◽  
High Dose ◽  
Toxicity Profile ◽  
Group 2

Abstract Abstract 32 Background: RIT based conditioning offers the potential of combining the efficacy of radiation with decreased toxicity over traditional TBI. In pilot trials we demonstrated that combining Yttrium 90 (ibritumomab tiuxetan) with high-dose BEAM (ZBEAM) is feasible and has a toxicity profile similar to high-dose BEAM. Herein we report the results of a comparative analysis designed to evaluate transplant outcomes among DLCL patients who were conditioned with either ZBEAM or a TBI-based conditioning regimen. Patients were matched on age (+/− 5 years), disease status, number of prior regimens, year of diagnosis (+/− 5 years), and year of transplant (+/− 5 years). There was a total of 92 DLCL patients treated from 01/1997-01/2009; 46 patients in each treatment group. The median patient age was 56.5 years (range: 19–78) for the ZBEAM group, and 53 years (range: 21–62) for the TBI group. Both groups had a median of two prior regimens, with 13% (ZBEAM) and 15% (TBI) considered high-risk first remission, 65% beyond 1st CR and 22% induction failures in each cohort. The median length of follow-up for surviving patients was 51–83 months. There was a trend toward improved PFS in the RIT group: 2 year PFS for ZBEAM group 66% (95%CI: 56–74) vs. 50% (95%CI: 43–57) for TBI group (p<0.08). Results to date show that a plateau in PFS appears to have been achieved for both groups (at 2.6 years in the ZBEAM group and 3.7 years for the TBI group), which translates into a 20% improvement in PFS for the ZBEAM patients, >4 years post transplant. Similarly the OS estimate was significantly higher for ZBEAM compared to TBI controls: 84% vs. 59 % (p<0.01). The lower OS rate for the TBI cohort was primarily due to toxicity, with a 2 year non relapse mortality of 0% for ZBEAM vs. 13% for TBI. (p<0.01) The causes of death included: relapse progression n=9 (ZBEAM), n=15 (TBI), infection n=2 TBI, cardiac disease n=2 TBI, pneumonia N= 1 TBI, unknown N=3 TBI. Conclusions: RIT based conditioning demonstrated improved survival when compared to traditional radiation based regimens in the treatment of DLCL due to a more favorable toxicity profile, while maintaining potent anti-lymphoma effects. Disclosures: No relevant conflicts of interest to declare.

Ibritumomab tiuxetan combined with high-dose chemotherapy and autologous stem-cell transplantation (SCT) in patients with chemo-refractory aggressive non-Hodgkin’s lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6538-6538
Author(s):  
A. Shimoni ◽  
T. Zwass ◽  
Y. Oksman ◽  
I. Hardan ◽  
N. Shem-Tov ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Large Cell ◽  
High Dose Chemotherapy ◽  
Aggressive Lymphoma ◽  
High Dose ◽  
Ibritumomab Tiuxetan ◽  
Bulky Disease ◽  
Conditioning Regimens ◽  
Refractory Lymphoma

6538 Background: High-dose chemotherapy and autologous SCT have an established role in the treatment of patients with first chemo-sensitive relapse of aggressive lymphoma. However, autologous SCT has only limited success when performed in refractory or progressive stage of the disease and the expected 1-year progression-free survival (PFS) in this setting is < 20%. Methods: This study was designed to explore the safety and outcome following inclusion of ibritumomab tiuxetan (IT) in the conditioning regimen given prior to autologous SCT. Patients were eligible for this study only if they had refractory lymphoma and a positive PET-CT prior to SCT. The primary end-point was 1-year PFS. Rituximab 250 mg/m2 followed by IT 0.4 mCi/kg were given on day -14. Chemotherapy according to standard BEAM was started on day -6. Results: The study included 20 pts, median age 55 years (range, 35–66). Histology was diffuse large cell (n=14), transformed follicular (n=5) and mantle cell lymphoma (n=1). Patients had active lymphoma at SCT, either primary refractory (n=11) or refractory relapse (n=9) and 12 had bulky disease at SCT. The median number of prior therapies was 3 (range, 1–6). There were no early infusion reactions associated with IT. Fourteen patients achieved CR, 4 achieved PR and 2 died early after SCT. With a median follow-up of 9 months (range, 1–20), 14 patients are alive and 6 have died with an estimated 1-year survival of 58% (95% C.I., 31–85). All surviving patients are progression-free. Only 2 patients relapsed with a 1-year cumulative incidence of only 14% (5–51). Two patients died of multi-organ toxicities and 2 of late occurring infections. These rates of non-relapse mortality are expected in heavily pretreated patients with refractory lymphoma and there was no additional toxicity related to IT. Conclusions: The inclusion of IT in the conditioning regimens given prior to autologous SCT may reduce the risk of relapse following autologous SCT and improve the poor outcome of patients with refractory lymphoma given SCT with standard conditioning regimens. This observation merits further study in larger comparative trials. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document