RIC Allogeneic Transplantation Improves the Overall and Progression- Free Survival of Hodgkin Lymphoma Patients Relapsing after Autologous Transplantation: A GITMO Retrospective Study Based on Time of HLATyping and Donor Availability

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 460-460
Author(s):  
Barbara Sarina ◽  
Luca Castagna ◽  
Fabio Benedetti ◽  
Francesca Patriarca ◽  
Michele Malagola ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Hla Typing ◽  
Rank Test ◽  
Donor Group ◽  
No Donor ◽  
Free Survival

Abstract Background: Hodgkin Lymphoma (HL) patients (pts) relapsing after autologous transplantation (auto-SCT) have a very poor outcome with no chemotherapy options able to obtain a long term disease control. Allogeneic stem cell transplantation (allo-SCT) employing reduced intensity conditioning (RIC) is increasingly used in lymphomas, but the number of studies in HL is quite limited, some groups reported conflicting results, and thus no clear evidence exists on its role as an effective salvage option in the clinical setting. Aims: We investigated the role of RIC allo-SCT in HL pts relapsing or progressing after auto-SCT (primary refractory patients were not included). Our study was structured similarly to an intent to treat analysis, and thus was based on the commitment of the attending physician to perform an allo-SCT. Only those pts undergoing a HLA-typing immediately after the failure of auto-SCT were included. The cohort of pts having a donor (donor group) was compared with the one not having a suitable donor (no donor group). Patients and Methods: 132 pts were retrospectively evaluated, for all of them a search for a sibling or matched unrelated donor (MUD) was started at the time of relapse/progression after auto-SCT. Seventy-five pts found a donor and 68 (90%) underwent an allo-SCT: 36 identical siblings (52%), 23 MUD (33%), 6 haploidentical family donors (9%). Thiotepa, cyclophosphamide and fludarabine containing regimens were used in all pts; GVHD prophylaxis was based on MTX and cyclosporine except for haploidentical-SCT. Seven pts having a donor did not receive allo-SCT for progressive disease. Pts not having a donor (n= 57) received chemo- and/or radiotherapy according to the standard policy of each center. The two cohorts of patients were well balanced in terms of clinical features, in particular the number of patients relapsing/progressing within 6 months from auto-SCT was similar. Results: The patient median age was 30 years (17–62). The median followup was 24 months. For all pts, the median overall (OS) and progression free survival (PFS) were 31 and 15 months, respectively. The 2-year OS and PFS were 56% and 29% respectively. The cumulative transplant-related mortality was 12% for the donor group. The 2-y OS and PFS were significantly better in the donor compared to the no donor group (OS 70% vs 38.8%, p 0.001, long rank test; PFS 42% vs 10%, p 0.03, long rank test). In multivariate analysis having a donor was statistically significant for OS and PFS. When we considered only the pts actually allografted, again the 2-years OS and PFS were significantly better compared to the no allo-group (OS 77% vs 35% and PFS 47% vs 9.3%). Acute GVHD grade II-IV occured in 17 pts (25)% and chronic GVHD in 27 pts ( 40%). In multivariate analysis, being in complete remission before allo-SCT significantly improved OS and PFS. Conclusions: This is the largest study comparing RIC allo-SCT vs conventional treatment in HL patients failing an auto-SCT. Allo-SCT is a feasible option and prolongs OS and PFS. As expected, the attainment of complete remission before allo-SCT improves the outcome.

scholarly journals Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability

Blood ◽  
2010 ◽  
Vol 115 (18) ◽  
pp. 3671-3677 ◽  
Author(s):  
Barbara Sarina ◽  
Luca Castagna ◽  
Lucia Farina ◽  
Francesca Patriarca ◽  
Fabio Benedetti ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Hodgkin Lymphoma ◽  
Autologous Transplantation ◽  
Multivariable Analysis ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Hla Typing ◽  
Human Leukocyte Antigen Typing ◽  
Leukocyte Antigen

Abstract Hodgkin lymphoma relapsing after autologous transplantation (autoSCT) has a dismal outcome. Allogeneic transplantation (alloSCT) using reduced intensity conditioning (RIC) is a salvage option, but its effectiveness is still unclear. To evaluate the role of RIC alloSCT, we designed a retrospective study based on the commitment of attending physicians to perform a salvage alloSCT; thus, only Hodgkin lymphoma patients having human leukocyte antigen-typing immediately after the failed autoSCT were included. Of 185 patients, 122 found an identical sibling (55%), a matched unrelated (32%) or a haploidentical sibling (13%) donor; 63 patients did not find any donor. Clinical features of both groups did not differ. Two-year progression-free (PFS) and overall survival (OS) were better in the donor group (39.3% vs 14.2%, and 66% vs 42%, respectively, P < .001) with a median follow-up of 48 months. In multivariable analysis, having a donor was significant for better PFS and OS (P < .001). Patients allografted in complete remission showed a better PFS and OS. This is the largest study comparing RIC alloSCT versus conventional treatment after a failed autoSCT, indicating a survival benefit for patients having a donor.

LMCE3 Treatment Strategy: Results in 99 Consecutively Diagnosed Stage 4 Neuroblastomas in Children Older Than 1 Year at Diagnosis

2000 ◽  
Vol 18 (3) ◽  
pp. 468-468 ◽  
Author(s):  
D. Frappaz ◽  
J. Michon ◽  
C. Coze ◽  
C. Berger ◽  
E. Plouvier ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Complete Remission ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Consolidation Therapy ◽  
French Society ◽  
Free Survival ◽  
Stage 4 ◽  
Total Body ◽  
Better Than

PURPOSE: To tailor postinduction therapy for stage 4 neuroblastoma in children who are older than 1 year at diagnosis according to status after induction. PATIENTS AND METHODS: From March 1987 to December 1992, 99 patients who were consecutively admitted were included in the Lyon-Marseille-Curie East of France (LMCE)3 strategy. After induction with the French Society of Pediatric Oncology NB87 regimen and surgery, patients who were in complete remission immediately proceeded to consolidation therapy with vincristine, melphalan, and fractionated total-body irradiation (VMT). All other patients underwent a postinduction strategy before VMT, either an additional megatherapy regimen or further chemotherapy with etoposide/carboplatin. RESULTS: The progression-free survival (PFS) is 29% at 7 years from diagnosis, which compares favorably with that of a similar cohort of 72 patients previously reported by our group (LMCE1; PFS of 20% at 5 years and 8% at 14 years, P = .004). In the multivariate analysis, only age younger than 3 years at diagnosis (P = .0085) and achievement of complete or very good partial remission after NB87 and surgery (P = .00024) remained significant. The PFS of the 87 patients who were included in the postinduction strategy was significantly better than that of the comparable 62 patients on the LMCE1 study (32% v 11% at 7 years; P = .005). CONCLUSION: The progressive improvements in the LMCE results over the last 10 years suggest that improvements in supportive care measures and increases in each component of this strategy (induction, postinduction, consolidation) may all contribute to increased survival rates.

Association of early tumor shrinkage with progression-free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 749-749
Author(s):  
Hiroshi Nakatsumi ◽  
Satoshi Yuki ◽  
Tetsuhito Muranaka ◽  
Hiraku Fukushima ◽  
Takashi Kato ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Tumor Shrinkage ◽  
First Line ◽  
Free Survival ◽  
Log Rank Test ◽  
Early Tumor Shrinkage ◽  
Significant Difference ◽  
Early Tumor

749 Background: It was reported that early tumor shrinkage (ETS) was associated with better overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) receiving cetuximab. We investigated association of ETS with progression free survival (PFS) in pts with unresectable colorectal liver metastases (CLM) from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety and so on. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. In this analysis, association of ETS at 8 weeks from the start of chemotherapy with pts characteristics, PFS and TTF was evaluated. Pts characteristics were compared using Student-t test, chi-square test and Fisher’s exact test. PFS and TTF were analyzed with Kaplan-Meier method and compared using log-rank test. Univariate analysis for the association of pts characteristics with PFS and TTF was performed using log-rank test, and multivariate analysis was performed using Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 74 pts with CLM were evaluable for ETS. Forty-nine pts (66.2%) had ETS ≥20%. The pts characteristics between ETS ≥20% and <20% were well balanced. The median PFS was 7.3 months in ETS <20% versus 10.0 months in ETS ≥20% (HR 0.55; p=0.025). In multivariate analysis for PFS, there was no significant difference between ETS ≥20% and <20% (HR 0.585; p=0.066). The median TTF (ETS <20% v ≥20%) was 5,1 months vs. 7.7 months (HR 0.46; p=0.003). In multivariate analysis for TTF, there was significant difference between ETS ≥20% and <20% (HR 0.509; p=0.017). Conclusions: In this analysis, ETS ≥20% might be positive predictive marker for PFS and TTF in pts with CLM receiving first-line BV-based chemotherapy.

The Impact of Lymphocyte Subset Recovery At 3 Months on Progression-Free Survival After Myeloablative Allogeneic Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4065-4065
Author(s):  
Junya Kanda ◽  
David A. Rizzieri ◽  
Gwynn D. Long ◽  
Cristina Gasparetto ◽  
John P. Chute ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Complete Remission ◽  
Progression Free Survival ◽  
Myelogenous Leukemia ◽  
Rank Test ◽  
Free Survival ◽  
Log Rank Test ◽  
Standard Risk

Abstract Abstract 4065 Background: Opportunistic infection and disease relapse due to a delayed or impaired cellular immune reconstitution following allogeneic stem cell transplantation (SCT) is associated with significant morbidity and mortality. Various lymphoid subsets have been suggested to play an important role in immune function. However, it remains unknown which of these subsets directly impact survival after SCT. Therefore, we prospectively quantified multiple lymphoid subsets at 3 months following myeloablative allogeneic SCT and evaluated their impact on progression-free survival (PFS). Methods: Quantitative recovery of 13 lymphoid subsets was prospectively characterized in a consecutive cohort of adult patients undergoing T-cell replete myeloablative SCT using peripheral blood stem cells (PBSCs) from a matched sibling donor (MSD) or a matched unrelated donor (MUD), or dual umbilical cord blood (DUCB) grafts. CD3+, CD4+, CD8+, regulatory (Treg) (CD4+, CD25+, CD62L+), cytotoxic (CTL) (CD8+, CD57+, CD28-), and activated T cells (CD8+, HLA-DR+), naïve CD4+ T cells with L-selectin expression (CD4+, CD45RA+/CD45RO-, CD62L+), NK (CD3-, CD16+/CD56+) and NKT cells (CD3+, CD16+/CD56+), B cells (CD19+, CD3-, CD16-, CD56-), plasmacytoid dendritic cells (DCs) (CD123+, CD11c-), and myeloid DCs (CD123-, CD11c+) were analyzed by flow cytometry on fresh peripheral blood. We included 69 patients (MSD, n = 23; MUD, n = 24; DUCB, n = 22) with standard-risk hematologic malignancies who survived at least 3 month (landmark day) following transplantation to evaluate the prognostic impact of lymphoid subset recovery at 3 months on PFS. Standard-risk diseases were defined as acute myelogenous leukemia (AML) in 1st or 2nd complete remission, acute lymphoblastic leukemia (ALL) in 1st or 2nd complete remission, myelodysplastic syndrome (MDS) with blasts <5%, malignant lymphoma (ML) in any complete remission, chronic myelogenous leukemia (CML) in 1st or 2nd chronic phase, and myelofibrosis (MF). PFS was defined as period from the 3 month after transplantation to disease progression or death, whichever occurred first and censored at time of last follow-up. The probability of PFS was estimated according to the Kaplan-Meier method, and groups were compared using the log-rank test. Cox proportional hazards multivariate regression modeling was used to predict PFS. Each lymphocyte subset was dichotomized at the median value and analyzed in a bivariate model adjusted for donor type (MSD/MUD or CBT) as well as in a univariate model in the MSD/MUD group. A parallel analysis was not performed in the CBT group due to few events. Results: Median age (range) of recipients was 40 (19–65) years. Primary diseases were AML (n = 42), ALL (n = 12), MDS (n = 8), CML (n = 4), ML (n = 2), and MF (n = 1). Tacrolimus-based GVHD prophylaxis was used in 83% of recipients. Median follow-up of survivors after transplantation was 21.1 (range, 3.9–53.6) months. PFS rate at 1 year among DUCB, MSD, and MUD recipients was 0.85 (95% confidence interval, 0.61–0.95), 0.64 (0.40–0.80), and 0.73 (0.49–0.86), respectively, without significant difference between the 3 groups (log-rank test, P = 0.164). Patient characteristics were not associated with PFS in the univariate analysis. In the bivariate analysis controlling for donor type, higher numbers of T cells (P = 0.016), Treg (P = 0.015), CTL (P = 0.041), and myeloid DC (P = 0.028) were significantly associated with improved PFS. In the MSD/MUD group, myeloid DC was the only significant variable (hazard ratio 0.25, 95% confidence interval, 0.07–0.89, P = 0.032) (Figure 1). Conclusion: Total T cell, regulatory T cell, cytotoxic T cell and myeloid DC recovery at 3 months post transplant is predictive of PFS. Given the unique properties of the DUCB graft, the predictive potential of lymphocyte subsets on PFS may differ from that of MSD/MUD transplant recipients and a larger cohort of DUCB recipients is needed to perform such an analysis. However, among recipients of MSD/MUD grafts, poor myeloid DC recovery at 3 months following transplantation predicted for worse PFS. These data allow for identification of a population at high risk for poor outcome who may be appropriate targets for intervention to augment post-transplant immune recovery using novel techniques. Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Conditioning Allogeneic Stem cell Transplantation (RIC-alloSCT) for Elderly Acute Myeloid Leukaemia (AML) Patients Over 60 Years: A “donor” Versus “no donor” Comparison

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2037-2037
Author(s):  
Pierre Peterlin ◽  
Emmanuel Raffoux ◽  
Patrice Chevallier ◽  
Thierry Guillaume ◽  
Thomas Gastinne ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Hla Typing ◽  
Donor Group ◽  
No Donor ◽  
Free Survival ◽  
Median Period ◽  
To Receive ◽  
Related Mortality ◽  
Acute Myeloid

Abstract Abstract 2037 Acute Myeloid Leukemia(AML) in elderly patients is associated with a poor outcome even for patients able to receive intensive chemotherapy. Relapse rate remain elevated around 60 to 80% at 3 years especially in case of unfavourable cytogenetics. From more than 10 years, the approach of RIC-alloSCT has permitted to extend the age limit of transplant in this population. However, feasibility remains controversial for patient aged of 60 years or more because of more frequent co-morbidities translating into an higher risk of treatment related mortality (TRM). To address the question of feasibility and results of RIC-alloSCT in AML patients of 60 years or more in a intend to treat manner approach, we have conducted a retrospective bi-centric analysis based on a comparison “donor” versus “no donor” for patient in first complete remission (CR1). Methods: 96 AML were included, all have received a 3+7 or equivalent induction regimen, between 2001–2009 in two different French centers and have benefited of an HLA typing in CR1. All patients of the “donor” group are considered for a RIC-alloSCT after one or two courses of consolidation. Results: The “donor” group is constitute of 30 patients with a median age of 65.5 years and with an HLA identical donor identified. Eighteen 60%) have been finally transplanted with a median period of 188 days from diagnosis to graft. The “no donor” group is constituted by 66 patients with a median age of 68.5. The two groups are similar considering cytogenetics risk and haematological features of the disease. Median follow up is 48 months for alive patients. No difference of overall survival (OS) or Leukemia free survival (LFS) has been observed between the ”donor” and “no donor group” (respectively 51% vs 44%, p=0.7 and 35%vs 32%, p=0.27). When restricting analysis to the patient who could actually received the RIC allo-SCT, the transplant group (n=18) has a significant better outcome for both OS and LFS as compared to the “non transplant” (n=78) group (69% vs 32% and 52% vs 29% respectively). In the transplant group, no patient died from transplant-related mortality. Acute and extensive chronic graft versus host disease (aGVHD and cGVHD) occurred respectively in 5/18 and in 8/18 patients of the “transplant” group. Conclusion: In a intend to treat manner, RIC-alloSCT provides similar outcome as compared to chemotherapy alone in this series of 96 patients. However, both OS and LFS are significantly improved for patients who have actually received RIC-alloSCT. Toxicity appears to be limited in the “transplant” group. Recruiting patients in this study is still ongoing and final results will be presented at the congress. Disclosures: No relevant conflicts of interest to declare.

The benefit of reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) as salvage treatment for relapsing multiple myeloma (MM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8045-8045
Author(s):  
M. Mohty ◽  
H. De Lavallade ◽  
C. Chabannon ◽  
A. Stoppa ◽  
C. Faucher ◽  
...  
Keyword(s):  
Disease Progression ◽  
Salvage Therapy ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Hla Typing ◽  
Donor Group ◽  
No Donor ◽  
Disease Response ◽  
Intention To Treat ◽  
Sibling Donor

8045 Background: The role of RIC allo-SCT in MM is still controversial. This single centre study aimed to evaluate RIC allo- SCT for relapsed MM, using a genetic randomization through a donor vs. no donor comparison. Methods: Between 2002 and 2005, 32 patients with relapsed or refractory MM, and with an identified sibling, were referred to our centre for HLA typing. In all, 19 patients (59%; donor group) had an HLA-identical sibling donor, while the remaining 13 pts (41%; no donor group) had no HLA-identical sibling donor. There were no significant differences between these two groups that were comparable as for demographic, disease and prognosis factors. All pts had previously failed auto-SCT. Results: Among the 19 pts from the donor group, 18 (95%) could proceed to allo-SCT. With a median overall FU of 36 m., 11 patients (85%; 95%CI: 54–98%) from the no donor group had disease progression despite salvage therapy, and only 6 of them are still alive, of whom 5 (80%) in progressive disease at last FU. In contrast, only 5 pts (28%;P=0.001) from the donor group progressed after RIC allo-SCT. In the RIC allo-SCT group, 10 pts (56%;95%CI;33–79%) are still alive, with 4 pts being in CR, and 5 in PR or VGPR. Only one patient is currently experiencing disease progression and receiving salvage therapy. Interestingly, 11 pts (61%;95%CI,39–83%) from the RIC allo-SCT group showed objective disease response, usually concurrent to chronic GVHD. In all, 6 pts died from TRM for an overall incidence of TRM of 33% (95%CI,11–55%) in this population of heavily pretreated and relapsed or refractory MM population. In an intention-to- treat analysis, the KM estimate of progression-free survival was significantly higher in the donor group as compared to the no donor group (P=0.01; 46% vs. 8% at 3 y.). Conclusions: RIC allo-SCT from an HLA-identical sibling is a feasible and potential therapy that should be proposed for refractory or relapsed MM, since a potent graft-vs. -MM effect can be induced despite heavy pretreatments, allowing for significantly longer PFS. Also, the latter results are expected to be further improved with the systematic and early use of maintenance therapies after RIC allo-SCT. No significant financial relationships to disclose.

Analysis of Kohne's prognostic index in KRAS wild-type patients with metastatic colorectal cancer (mCRC) treated with salvage-line cetuximab-based regimen: HGCSG0901.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 634-634
Author(s):  
Ayako Doi ◽  
Satoshi Yuki ◽  
Yasushi Tsuji ◽  
Takahide Sasaki ◽  
Hiraku Fukushima ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Prognostic Impact ◽  
Wild Type ◽  
Free Survival ◽  
Significant Difference

634 Background: In the treatment for mCRC, it is essential for understanding the prognosis of each individual patient. Köhne’s index (KI) based on performance status, white blood cell count, alkaline phosphatase and number of metastatic sites has been previously proposed. However, in the salvage setting, the validity of KI has not been reported in patients treated by cetuximab-based chemotherapy. Methods: 269 patients with mCRC treated by cetuximab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS wild-type patients who were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. The analysis was also designed to determine whether the Köhne’s classification could be extended to other endpoints such as progression-free survival. Results: All data were available for prognostic categorization in 127 patients. Median overall and progression-free survival was 9.8 and 4.2 months. The distribution and median survival / progression-free survival for KI were as follows: low risk (L) (n = 40; 13.1/5.1 months), intermediate risk (I) (n = 17; 9.6/3.5 months), and high risk (H) (n = 70; 7.6/4.1 months). For overall survival, there was significant difference between L and H (p = 0.004), but not between L and I (p = 0.213), and between I and H (p = 0.321). For progression-free survival, there was tended to difference between L and H (p = 0.083), but not between L and I (p = 0.392), and between I and H (p = 0.630). In Cox multivariate analysis, KI showed an independent prognostic impact (HR 1.370, p = 0.010), but not predictive impact (HR 1.147, p = 0.212). Conclusions: In this analysis, KI might be a prognostic factor in salvage treatment with cetuximab-based regimen, but no effect predicted impact. Moreover, the prospective evaluation is needed for the further validation.

scholarly journals Simplified Validated Prognostic Model for Progression-Free Survival after Autologous Transplantation for Hodgkin Lymphoma∗

2013 ◽  
Vol 19 (12) ◽  
pp. 1740-1744 ◽  
Author(s):  
Theresa Hahn ◽  
Philip L. McCarthy ◽  
Jeanette Carreras ◽  
Mei-Jie Zhang ◽  
Hillard M. Lazarus ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Prognostic Model ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Free Survival
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