Reduced-Intensity Conditioning for Allograft (RICT) after Cytoreductive Autograft (ASCT) in Relapsed/Resistant Hodgkin’s Lymphoma (HL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3294-3294
Author(s):  
A. M. Carella ◽  
E. Todisco ◽  
L. Castagna ◽  
A. Santoro ◽  
G. Catania ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Complete Remission ◽  
Long Term Results ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
High Dose Therapy ◽  
Previous Therapy ◽  
Reduced Intensity

Abstract Reduced-intensity conditioning for transplant (RICT) aims to exploit graft vs lymphoma (GvLy) effects while reducing conditioning-related toxicity. Because GvLy responses might be insufficient when HL are bulky and lymphoma growth is rapid, we pionered that intensive cytoreduction prior to RICT may allow GvLy reaction to be exploited (Carella et al. JCO2000; 18:3918). Thirty-eight patients with relapsed (n=26) or refractory (n=12) HL underwent RICT from an HLA-identical sibling preceeded by ASCT. Previous therapy consisted of 2–6 lines. High-dose therapy with ASCT consisted of BEAM protocol (n=29) or melphalan 200 mg/m2 (n=9). RICT consisted of fludarabine-cyclophosphamide (n=30) or fludarabine-melphalan (n=8). The two groups had similar prognostic factors. The median time to neutrophils and platelets recovery was 10 days and 16 days, respectively. Chimerism studies indicated 100% donor-derived engraftment. Day 100 and cumulative (2 yrs) TRM were 5,3 % (2 pts) and 18% (7 pts), respectively. Seventeen patients (44%) are alive (12 in complete remission and 5 with stable disease) with a median follow-up of 41 months (7–110 months). Twenty-one patients expired (TRM n=7, disease progression n=14). In conclusion, tandem ASCT/RICT is feasible and effective salvage therapy for patients with advanced HL. The long-term results obtained appear encouraging.

Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD.

1997 ◽  
Vol 15 (2) ◽  
pp. 528-534 ◽  
Author(s):  
V Bonfante ◽  
A Santoro ◽  
S Viviani ◽  
L Devizzi ◽  
M Balzarotti ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Complete Remission ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Response Duration ◽  
Long Term Results ◽  
High Dose ◽  
First Line ◽  
Disease Extent

PURPOSE This study analyzed long-term results in patients with Hodgkin's disease who were resistant to or relapsed after first-line treatment with MOPP and ABVD. Response to salvage treatments and prognostic factors were also evaluated. PATIENTS AND METHODS The study population included 115 refractory or relapsed patients among a total of 415 patients treated with alternating or hybrid MOPP-ABVD followed by radiotherapy (25 to 30 Gy) to initial bulky sites. The median follow-up duration of the present series was 91 months. Thirty-nine of 115 patients (34%) showed disease progression while on primary treatment (induction failures); 48 relapsed after complete remissions that lasted < or = 12 months and 28 after complete remission that lasted more than 12 months from the end of all treatments. RESULTS At 8 years, the overall survival rate was 27%, being 54% and 28% in patients whose initial complete remission was longer or shorter than 12 months, respectively, and 8% in induction failures (P < .001). Response to first-line chemotherapy and disease extent at first progression significantly influenced long-term results, as well as the incidence and duration of complete remission. CONCLUSION The present data confirm previous observations that showed the main prognostic factors to influence outcome after salvage treatment are response duration to first-line therapy and disease extent at relapse. The results indicate that patients who relapse after the alternating MOPP/ABVD regimen have a prognosis similar to that of patients who relapse after a four-drug regimen (MOPP or ABVD alone). Re-treatment with initial chemotherapy seems the treatment of choice for patients who relapse after an initial complete remission that lasts greater than 12 months, while the real impact of high-dose chemotherapy or new regimens should be assessed in resistant patients.

Long-term results in multiple myeloma treated with high-dose melphalan and autologous peripheral stem cell transplantation and achieving complete remission.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18564-e18564
Author(s):  
Massimo Vincenzo Martino ◽  
Maurizio Postorino ◽  
Giuseppe Alberto Gallo ◽  
Giuseppe Irrera ◽  
Eugenio Piro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Long Term Results ◽  
Cumulative Probability ◽  
High Dose ◽  
Probability Of Survival ◽  
High Dose Melphalan

e18564 Background: Major progress has been made in the treatment of multiple myeloma (MM) in recent years, including the introduction of novel agents and transplant strategy. High-dose melphalan (HDM) followed by autologous haematopoietic stell cell transplantation (AHSCT) remains an integral component of upfront treatment strategy. Many studies stress the importance of achieving a deeper response as a surrogate for improved survival but, despite the improvements, MM remains incurable and long-term survival appears elusive. The aim of study is to establish the actual prognosis for the different response categories in the same original cohort of patients with MM treated with HDM and AHSCT after long-term follow-up. Methods: We evaluated a cohort of MM patients treated up-front in the Bone Marrow Transplant Unit of Reggio Calabria between 1994 and 2006. Disease response was assessed with the use of criteria from the European Group for Blood and Marrow Transplantation modified to include Complete Remission (CR) and near Complete Remission (nCR). Results: The study group was composed by 150 patients (age at 1st AHSCT M±SD 55±9 years, male 64%); 94 (63%) of them had 2 AHSCT. After treatments 22 (15%) patients have a CR, 32 (21%) a nCR and 90(64.0%) a PR. After a mean follow up of 50 months the cumulative probability of survival was 69% for patients with CR, 43% for those in nCR and 0% for patients in PR (log-rank test P PR vs nCR=0.006; CR vs nCR and nCR vs PR<0.001 ). The estimate mean survival for patients with CR, nCR and PR was respectively 166, 81 and 46 months. For patients with CR the survival curves showed a plateau of cumulative probability of survival after 134 months. Conclusions: In MM achieving a CR after HDM and AHSCT is a central prognostic factor. The relapse rate is low in patients with >11 years of follow-up, possibly signifying durable remission in patients in CR.

Reduced Intensity Conditioning Regimen for Allografting Following Autografting Has Strong Anti-Myeloma Activity and Delays Disease Progression Compared to Tandem Autografting.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 51-51
Author(s):  
A.M. Carella ◽  
E. Lerma ◽  
S. Nati ◽  
A. Congiu ◽  
E. Rossi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Disease Progression ◽  
Remission Rate ◽  
Conditioning Regimen ◽  
Complete Remission Rate ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
High Dose Therapy ◽  
Reduced Intensity

Abstract Multiple Myeloma (MM) is still an incurable disorder despite the numerous attempts to exploit new therapy approaches for it. The better understanding of its molecular pathogenesis has led to the development of effective, novel therapeutic agents like thalidomide and the proteasome inhibitor bortezomib. High-dose therapy with stem cell transplantation and novel targeted therapies represent two approaches to overcome resistance of multiple myeloma cells to conventional treatments. Autografting (AutoSCT) has been limited by high-relapse rates and conventional allografting (AlloSCT) by excessive TRM and toxicity. 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. 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. Our data demonstrated that RICT following an AutoSCT can mediate a potentially curative graft-versus-myeloma effect and 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 number of 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 AutsoSCT Melphalan (200mg/m2) Melphalan (200mg/m2) Conditioning regimen for RICT --- TBI/Fludarabine Median days from AutoSCT to RICT --- 80 Complete Remission rate 14% 50% Disease-free Survival at 4 yrs 14% 45% Overall Survival at 4 yrs 28% 40% Transplant-Related Mortality 0% 0%

Long Term Results of Fludarabine/Melphalan as Reduced Intensity Conditioning Regimen (RIC) for Transplantation in Mantle Cell Lymphoma (MCL): Age Matters

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4388-4388
Author(s):  
Jorge Gayoso ◽  
Rodrigo Martino ◽  
Pascual Balsalobre ◽  
Javier De la Serna ◽  
José Francisco Tomás ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Long Term Results ◽  
Mixed Chimerism ◽  
Reduced Intensity Conditioning ◽  
Who Grade ◽  
Reduced Intensity

Abstract Introduction: Myeloablative allogeneic stem cell transplantation in patients (pts) with MCL has been traditionally used only in young pts without co-morbidities due to its high toxicity. During the last 10 years, many different reduced intensity conditioning (RIC) regimens have been introduced into clinical practice trying to reduce this toxicity, preserving the establishment of a meaningful graft-tumor effect (GVT). However, few homogeneus pts series have been reported focused on MCL, with encouraging results in some studies. Thus, we report herein the outcome of 18 consecutive MCL pts who received an allo-PBSC-RIC from an HLA-identical sibling donor with a long follow-up. Patients and methods: The RIC consisted in iv fludarabine 125–150 mg/m2 from day-8 to -4 and iv melphalan 80 or 140 mg/m2 on day-3 to -2. Rituximab 375 mg/m2 was added to RIC in 8 pts on days-9, +1, +8 and +15. GVHD prophylaxis consisted in standard cyclosporine and methotrexathe. Gradual cyclosporine tappering from day +50 was initiated if mixed chimerism or persistent disease were present. We focus on engraftment kinetics, early toxicities, non-relapse mortality (NRM), chimerism kinetics, GVHD as well as estimated anti-tumoral efficacy, progression-free and overall survival (PFS and OS). Results: 18 MCL pts were included from 2000 to 2008, with a median follow-up of 50 months. Median age was 56 years (range: 43–68), 13 were males, with a median pre-RIC treatment lines of 2 (1–4) including 2 autoHSCT. Before alloRIC, 13 pts (72%) were in 1st or later CR, while 5 pts (28%) were in chemo-sensitive PR. Median CD34+/kg infused cells were 5,8 ×106 (4,3–10,8) and 2,0 ×108 (0,7–4,1) CD3+ lymphocytes/kg. All pts engrafted, reaching ANC&gt;500 on day +16 (13–20) and platelets&gt;20.000 on day +12 (8–32), with no graft failures. Early toxicity (&lt;day +100) included WHO grade 3–4 mucositis in 8 (44%), febrile neutropenia in 6 (33%) and bacterial infections in 4 (22%) with 2 deaths (1 varicella-zoster encephalitis and 1 refractory acute GVHD). There were 2 other deaths during the 1st year, both due to infections in the setting of extensive chronic GVHD, for a 1-year NRM of 22%. Complete donor T-cell chimerism (CC) was present at day +30 in 71% of evaluated pts and in 100% pts at day +90. Acute grade II–IV GVHD ocurred in 39% of pts at risk, with 17% of grade III–IV. Chronic GVHD affected 12/16 pts (75%), wich was extensive in 6 (38%). Only 1 patient (trasplanted in PR after 2 treatment lines) relapsed (6%). The 5-year estimated PFS and OS were both 77% (CI95%=58–97%) and 14 pts remain alive in CR. The only apparent prognostic factor in our study is age: 8 pts aged 60 or older have an OS of 33,3% vs 100% for the 10 pts younger than 60 years (p&lt;0.001). Conclusions: AlloRIC with fludarabine and melphalan in MCL pts offers a good toxicity profile, with high engraftment rate and good long term disease-free survival, especially in pts younger than 60. The very low long-term relapse rate seen in the context of a high incidence of chronic GVHD supports the continued sensitivity of MCL to a GVT effect. Figure Figure

High-Dose Therapy With Autologous Bone Marrow Support as Consolidation of Remission in Follicular Lymphoma: Long-Term Clinical and Molecular Follow-Up

2000 ◽  
Vol 18 (3) ◽  
pp. 527-527 ◽  
Author(s):  
John Apostolidis ◽  
Rajnish K. Gupta ◽  
Demetrios Grenzelias ◽  
Peter W. M. Johnson ◽  
Vassiliki I. Pappa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
Acute Myeloblastic Leukemia ◽  
Long Term Results ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Igh Rearrangement

PURPOSE: To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)–detectable Bcl-2/IgH rearrangements. PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow was treated in vitro with anti–B-cell antibodies and complement. RESULTS: Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four “early” and 10 “late” deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P = .04) and three or fewer treatment episodes before HDT (HR, 0.03; P = .001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up was associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P < .001) and death (HR, 0.25; P = .02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome. CONCLUSION: Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting.

Long-term results of high-dose chemotherapy (HDCT) supported by hematopoietic circulating (ASCT) or bone marrow (BMT) stem cell autografting as first salvage treatment for refractory or relapsed Hodgkin’s lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7567-7567
Author(s):  
S. Viviani ◽  
V. Bonfante ◽  
M. Di Nicola ◽  
S. Cortelazzo ◽  
C. Carlostella ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Dose Chemotherapy ◽  
Stage Iii ◽  
Long Term Results ◽  
Late Relapse ◽  
High Dose ◽  
First Line ◽  
Early Relapse

7567 Background: The aim of this retrospective study was to evaluate with a long follow-up the efficacy of HDCT + ASCT or ABMT for refractory or relapsed HL. Methods: Data were collected from 99 pts who failed or relapsed after first-line CT± radiotherapy and were treated with HDCT+ASCT or ABMT between Oct 1984 and Dec 2003. Thirty-two pts had late relapse (CR≥12 months), 31 had early relapse (CR<12 months), while 36 had primary refractory (IF) HL.The main pts characteristics at relapse/progression were as follows: M/F: 50/49; median age 28 years; stage III-IV:54%; B symptoms: 33%; bulky disease 22%; extranodal ± nodal disease 54%; IPI≥3 39%. HDCT program consisted in a debulking phase with sequential high-dose chemotherapy (Cyclophosphamide 7gr/mq followed by ASC or BM harvest, Methotrexate 8 gr/mq+ Vincristine 1.4 mg/mq, VP16 2 gr/mq) in 71 cases; 3–4 courses of Ifosfamide (3gr/mq × 4 days)+ Vinorelbine (25mg/mq day 1+5) in 28 cases. Final myeloablative course was BEAM (63%), or high-dose Melphalan combined with high-dose Mitoxantrone (11%) or with high-dose Carmustine (9%) or TBI (17%) followed by ABMT or ASCT. Results: Ninety-two pts (93%) completed the HDCT program, while seven pts (7%) progressed during debulking CT. Early and late toxicity were mild. After a median follow-up of 66 months both 10-year freedom from second progression (FF2P) and overall survival (OS) were 61% for all pts. FF2P and OS were respectively 70% and 66% for pts with late relapse; 64% and 60% for pts with early relapse; 52% and 56% for primary refractory pts. Multivariate analysis showed that prognostic factors for FF2P were stage III-IV vs I-II (HR 2.09; p=0.04), response to first-line CT: CR≥12 vs CR<12 vs IF (HR 2.19; p=0.058) and bulky vs non bulky (HR 1.96; p=0.07). Prognostic factors for OS were response to first-line CT (HR 2.59; p=0.05), stage III-IV vs I-II (HR 1.37; p=0.39) and bulky vs non bulky (HR 2.06; p=0.06).Conclusion: These long-term results confirm that HDCT + ASCT or ABMT was feasible, safe and very effective for the treatment of relapsed/refractory HL.Our data support the use of this strategy for the salvage therapy even in the unfavourable group of primary refractory pts. No significant financial relationships to disclose.

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