Gemcitabine and Oxaliplatinum (GemOx): An Effective Regimen in Patients with Refractory and Relapsing Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4845-4845
Author(s):  
Antonio Gutierrez ◽  
Jose Rodriguez ◽  
Andres Lopez ◽  
Jordi Martinez-serra ◽  
Jorge Gines ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
Grade 3

Abstract Abstract 4845 Hodgkin lymphoma (HL) represents 10–15% of all types of lymphoma. At present, more than 70% of patients can be cured with current strategies based on chemotherapy with or without radiotherapy. However, one third of the cases finally relapses and needs salvage regimens usually consolidated with high dose chemotherapy and autologous stem cell transplantation. The number of regimens and drugs available are limited and new protocols that increase the efficacy with manageable toxicity are needed. In the present communication we report the results of a retrospective study using the GemOx schema that combines the efficacy of gemcitabine in Hodgkin lymphoma with oxaliplatin, a less toxic and effective platinum-based drug. Patients and methods: Patients were eligible for this retrospective study, according to the following criteria: diagnosis of HL, which relapsed or failed to achieve complete remission after induction treatment. They received GemOx regimen that consisted of gemcitabine 1000mg/m2 and oxaliplatin 100mg/m2 on day 1. Treatment was given every 15 days if feasible or every 21 days. To evaluate response and toxicity Cheson criteria and OMS toxicity scale were used respectively. Results: Between 2003 and 2012, 29 patients with Hodgkin lymphoma were retrospectively included in this study. All patients had recurrent (n=17) or refractory (n=12) disease. Median age was 24 (14–76) years and 50% had an International Prognosis Score (IPS) higher than 2. Patients received a mean of 2.79 previous regimens and 79% more than 1 regimen before GemOx with 48% relapsing after a prior autologous stem cell transplant (ASCT). Median follow-up was 41 months. 76% of patients responded (31% complete responses; CR). Responses were better in the relapsed setting or partial response (PR) (85% with a 45% of CR) compared to the truly refractory cases (55% PR) (p=0.037). Main prognostic factors for HL were assessed to view their impact on survival. Factors related with progression- free survival (PFS) and overall survival (OS) were age lower than 45 years, response to GemOx and consolidation with stem cell transplantation (p=0.001). Presence of B-symptoms at diagnosis also influenced OS. Neurologic toxicity was present in 9% of patients, all of them grade I or II. Hematologic toxicity was also common, including grade 3 or 4 neutropenia in 23% of patients, and grade 3 or 4 thrombocytopenia in 33%. Nausea and vomiting occurred in all the patients at grade 2, or lower. At last follow-up, 13 patients (45%) are alive and remain free of progression. However, 16 patients (54%) had died: 12 (41%) due to progression of disease, 3 (10%) due to complications due to a subsequent allogenic transplant (graft versus host disease, thrombotic thrombocytopenic purpura and bleeding) and 1 due to pneumonia. PFS was better in patients consolidated with autologous or allogeneic transplantation (100%) compared with patients not consolidated (14%) (p=0.009). PBSC collection after GemOx and G-CSF was successful for all of candidates. Conclusions: 1) GemOx regimen is effective in relapsed or refractory Hodgkin lymphoma with manageable toxicity; 2) Results are better in relapsed or chemosensitive disease compared to truly refractory cases; 3) No mobilization failures were observed; 4) Consolidation after response is needed. Disclosures: No relevant conflicts of interest to declare.

A Phase II Study of Myeloablative I-131-Anti CD-20 (Tositumomab) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Adults ≥60 Years of Age with High-Risk Relapsed or Refractory B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 487-487 ◽  
Author(s):  
Ajay K. Gopal ◽  
Joseph G. Rajendran ◽  
Ted A. Gooley ◽  
John M. Pagel ◽  
Darrell R. Fisher ◽  
...  
Keyword(s):  
Older Adults ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Phase Ii ◽  
High Dose ◽  
Grade 3

Abstract The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet many are denied potentially curative high-dose regimens due to concerns of excessive toxicity with stem cell transplantation in this age group. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be ideal for older adults requiring high-dose therapy. We have treated 24 patients with relapsed or refractory B-cell NHL aged ≥60 years using high-dose I-131-tositumomab (GlaxoSmithKline) and ASCT on a phase II trial. Patients were required to have a performance status of 0–1, acceptable organ function, ≥2x106 CD34+ cells/kg collected, and <20 Gy prior radiation to critical organs. Patients with splenomegaly or tumor bulk over 500cc were required to undergo further cytoreduction or splenectomy in order to optimize biodistribution of the radiolabeled antibody. Patients without evidence of disease at the time of therapy were excluded. All pts underwent outpatient dosimetry using tositumomab (1.7 mg/kg) labeled with 5–10mCi I-131 followed by serial quantitative gamma camera imaging and patient and organ-specific dosimetry. Patients then received individualized infusions of I-131-tositumomab (1.7 mg/kg) to deliver 25–27Gy to the critical normal organ receiving the highest radiation dose followed by ASCT. Between 12/1/99 and 4/29/05 24 pts were enrolled on this study. Baseline characteristics included: median age at ASCT = 64 yrs (range 60–76 yrs), male = 15/24, median number of prior regimens = 4 (range 2–14), chemoresistant disease (defined as < a partial response to the most recent regimen) = 13/24, Stage III/IV=100%, >1 extranodal site = 21%, elevated LDH at treatment = 46%, IPI score at transplant 3–5 = 46%, Histology: diffuse large B-cell (DLBCL)=9 pts (with 4/9 transformed from follicular lymphoma [FL]), mantle cell (MCL)=8 pts, FL=6 pts, and marginal zone (MZL) 1 pt. The median I-131 activity administered was 525 mCi (range 328–1154 mCi) with dose limiting organs being lung, liver, and kidney in 12, 8, and 4 patients, respectively. The therapy was well tolerated with no treatment-related deaths, and no grade 3–4 Bearman toxicity. NCI CTC non-hematopoeitic toxicities by day 100 included: Grade 4=2/24 and Grade 3=17/24. The median time after ASCT for recovery of platelets > 20K and neutrophils >500 was 10 and 15 days, respectively. Sixteen of 24 pts remain alive (67%) and 10 (42%) are alive and progression-free with a median follow up from ASCT of 2.2 yrs (range 1 mo.–4.9 yrs.) for survivors. The estimated 3-year overall and progression-free survival are 56% and 37%, respectively. Surviving patients include 6/8 with MCL, 5/7 with FL/MZL, and 5/9 with DLBCL as well as 9/13 with chemoresistant disease. Myeloablative I-131-tositumomab with ASCT is a well-tolerated and effective transplant option for older adults with high-risk, relapsed B-NHL, though longer follow-up and additional pts will be needed to confirm the reproducibility and durability of these findings.

Allogeneic Stem Cell Transplant Versus Tandem High-Dose Melphalan for Front-Line Treatment of Deletion 13q14 Myeloma – An Interim Analysis of the German DSMM V Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 51-51 ◽  
Author(s):  
Stefan Knop ◽  
Peter Liebisch ◽  
Holger Hebart ◽  
Ernst Holler ◽  
Monika Engelhardt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Interim Analysis ◽  
Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
High Dose Melphalan

Abstract Abstract 51 Background Allogeneic stem cell transplantation (allo SCT), a treatment modality based on transfer of immunocompetent donor lymphocytes offers curative potential to subjects with a variety of hematological cancers. In multiple myeloma (MM), high-dose melphalan followed by autologous stem cell transplantation (auto SCT) is adopted as a standard of care. However, it remains palliative since virtually all patients (pts) relapse and renders allo SCT an option of interest. Deletion of chromosome 13q14 (13q-) in MM has been shown to negatively impact prognosis. Therefore, improvement of therapy for 13q- pts is highly desirable. Patients and methods A prospective two-arm multi-center trial (DSMM V) was set up by our group to compare tandem high-dose melphalan 200 mg/m2 (HD Mel) with a reduced intensity conditioning allo-SCT after one cycle of HD Mel for 13q- MM. Eligibility criteria were 13q- on bone marrow FISH analysis; age up to 60 years; newly diagnosed MM in Salmon and Durie stages II and III; and measurable disease. Allocation to either treatment arm was by availability of an HLA-matched (one mismatch allowed) volunteer related (VRD) or unrelated donor (VUD). Initially, all pts received four cycles of anthracycline/dexamethasone-based induction followed by chemomobilization of peripheral blood stem cells (PBSCT) and one cycle of HD Mel. Allogeneic SCT was performed after preparation with fludarabine (30 mg/m2 for 3 consecutive days) and melphalan 140 mg/m2. ATG was administered for VUD transplants. Results 199 pts with a median age of 53 (range, 30 – 60) years were enrolled between October 2002 and March 2007 and included in this interim analysis. Sixty-seven percent had stage III disease. Allo SCT was performed in 126 of 199 pts (63%), 76 of whom (60%) received VUD allografts. The remaining 73 subjects uniformely received tandem HD Mel. Pts following allo SCT were more likely to achieve CR (59%) when compared to tandem HD Mel (32%; p=.003) within one year after end of therapy. Similarly, overall response rate was significantly higher with allo SCT (91% versus 86%; p=.003). Of note, depth of response to allo SCT was not associated with presence of acute graft-versus-host disease (GVHD): 62% CR with grades II to IV GVHD vs 58% CR with grades 0 and I (p=.75). Treatment-related mortality (TRM) at 2 years from allo SCT was 16/126 (12.7%). At a median follow up of 25 months for tandem HD Mel and 34 months for allo SCT, projected 3-year overall survival is 72% (auto) and 60% (auto/allo SCT; p=0.22), respectively. Conclusions This is the largest trial on first-line allogeneic stem cell transplant in MM so far. Our interim results show a higher CR rate in FISH 13q- subjects undergoing allo SCT when compared to tandem HD Mel. Despite a majority of allografts in our study being delivered from unrelated donors, TRM was comparable to trials confined to sibling transplants. At a relatively short follow-up, there is not yet a difference between both arms regarding OS, albeit longer follow-up may be important as previously described. This as well as analysis of the impact of donor type and chronic GVHD on outcome will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Update on Salvage Options in Relapsed/Refractory Hodgkin Lymphoma after Autotransplant

ISRN Oncology ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Nida Iqbal ◽  
Lalit Kumar ◽  
Naveed Iqbal
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Clinical Success ◽  
Treatment Plan ◽  
Treatment Options ◽  
High Dose ◽  
Cell Transplant

Despite a high clinical success, relapse in Hodgkin lymphoma occurs in 10–30% of cases and 5–10% patients are nonresponsive to initial chemotherapy. The standard management of these patients includes high-dose chemotherapy followed by autologous stem cell transplant. However, 50% of patients ultimately relapse after autotransplant which poses a big challenge. Allogeneic stem cell transplantation offers the only chance of cure in these patients. For patients who are not candidates for allogeneic stem cell transplantation, achieving cure with other possible options is highly unlikely, and thus the treatment plan becomes noncurative. Various novel agents have shown promising results but the duration of response is short lived. A standard approach to deliver the most effective treatment for these patients is still lacking. This review focuses on the treatment options currently available for relapsed and refractory disease after autotransplant.

scholarly journals Checkpoint Inhibition Therapy in Transplant-Ineligible Relapsed or Refractory Classic Hodgkin Lymphoma

2021 ◽  
Vol 17 (2) ◽  
pp. 64-71
Author(s):  
Samer A. Al-Hadidi ◽  
Hun Ju Lee
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
High Dose ◽  
Cell Transplant ◽  
Classic Hodgkin Lymphoma

The checkpoint inhibitors nivolumab and pembrolizumab are principal treatment options for relapsed or refractory classic Hodgkin lymphoma. In patients who decline autologous stem-cell transplantation or who are unsuited for high-dose chemotherapy and subsequent autologous stem-cell transplantation because of comorbidities, the use of checkpoint inhibitors may improve overall survival and have a manageable side effect profile. This clinical review provides an evidence-based summary to guide practicing oncologists in the use of checkpoint inhibitors in relapsed or refractory classic Hodgkin lymphoma and includes checkpoint inhibitor efficacy and adverse effect profiles. We highlight the use of checkpoint inhibitors in the management of relapsed or refractory classic Hodgkin lymphoma in patients who are ineligible for an autologous stem-cell transplant with the goal of improving disease control while limiting adverse events.

Non-Myeloablative vs. Conventional Allogeneic Hematopoietic Stem Cell Transplantation for Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1132-1132
Author(s):  
Brad Pohlman ◽  
Tao Jin ◽  
Elizabeth Kuczkowski ◽  
Stacey Brown ◽  
Ronald Sobecks ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem

Abstract Non-myeloablative allogeneic stem cell transplantation (NMT) is increasingly used as an alternative to conventional bone marrow transplantation (BMT). Limited NMT data is available for lymphoma patients (pts). Most series include all hematological malignancies and only a minority with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL). Therefore, we reviewed the Cleveland Clinic BMT Program experience with lymphoma pts and specifically compared the outcome between NMT and BMT. Between July 2, 1985 and December 7, 2004, 67 pts received a matched related (n=47) or unrelated (n=20) donor BMT (n=46) or NMT (n=21) for HL (n=11), aggressive NHL (n=32), indolent NHL (n=23), or unknown NHL (n=1). Pts with lymphoblastic, Burkitt, or atypical Burkitt-like lymphoma were excluded. Compared to BMT pts, NMT pts were older, had longer time from diagnosis to transplant (tx), and were more likely to have a normal LDH and be in remission (CR/PR) at tx. The median follow-up of surviving BMT and NMT pts was 73.8 (range 11.8–106.7) and 20.6 (range 2.8–44.0) months, respectively. 18 (39%) BMT and 5 (24%) NMT pts progressed, and 9 (20%) BMT and 2 (10%) NMT pts died from lymphoma. The incidence of grade 2–4 acute GVHD was not different between the BMT and NMT groups. Among all pts, the risk of lymphoma progression was significantly higher in pts with compared to pts without GVHD (Figure 1). The overall survival for NMT pts was significantly better than for BMT pts (P=.019). Among 15 pts that previously received high dose therapy with autologous stem cell transplant (ASCT), all 7 BMT pts died a median of 1 (range 1–14) month post-BMT while 4/8 NMT pts remained alive 8, 21, 29, and 33 months post-NMT. By multivariate analysis, BMT (HR 7.74, 95% CI 2.49–24.0, P<.001), HL (HR 6.52, 95% CI 2.04-20-85, P=.002), prior ASCT (HR 3.33, 95% CI 1.20–9.25, P=.021), and increasing age by decade (HR 1.7, 95% CI 1.11–2.62, P=0.14) were associated with a significantly higher mortality while CR/PR at tx was associated with a significantly lower mortality (HR 0.44, 95% CI 0.21–0.93, P=.032). Restricting the multivariate analysis to the 56 NHL pts identified no significant independent prognostic factors. Finally, excluding the 15 pts with prior ASCT showed that BMT, >3 prior chemotherapy regimens, tumor >10 cm at diagnosis, older age, and no remission at tx were all associated with a significantly higher mortality. We conclude that: 1) lymphoma progression and lymphoma- or transplant-related death beyond 2 years are uncommon; 2) BMT after failed ASCT is uniformly fatal while NMT (even after failed ASCT) may lead to long-term survival; 3) GVHD (with its presumed graft vs. lymhoma effect) is important for long-term, progression-free survival; 4) compared to BMT, NMT is associated with a better OS (although pt selection may account for some of the observed difference), and 5) both NMT and BMT are appropriate options for selected NHL pts. Whether NMT or BMT offers any benefit compared to ASCT for HL pts is unclear. Figure Figure

scholarly journals Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center

2021 ◽  
Vol 27 ◽  
Author(s):  
A. Kopińska ◽  
A. Koclęga ◽  
A. Wieczorkiewicz-Kabut ◽  
K. Woźniczka ◽  
D. Kata ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Disease Status ◽  
Term Survival ◽  
Entire Cohort

Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach.Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting.Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18–44) underwent allo-SCT between 2002 and 2020.Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%.Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.

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