scholarly journals Value of autologous stem cell transplantation with purged bone marrow as first-line therapy for follicular lymphoma with high tumor burden: a GOELAMS phase II study

2000 ◽  
Vol 26 (9) ◽  
pp. 971-977 ◽  
Author(s):  
Ph Colombat ◽  
P Cornillet ◽  
E Deconinck ◽  
JM Tourani ◽  
M Gardembas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Autologous Stem Cell Transplantation ◽  
Phase Ii Study ◽  
Tumor Burden ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

High-Dose Bi-Weekly THP-COP Induction Treatment Followed by High-Dose Therapy with Autologous Peripheral Blood Stem Cell Transplantation for Advanced-Stage Follicular Lymphoma as First-Line Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5207-5207
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Masutaka Higashimura ◽  
Akihito Momoi ◽  
Nobuhiro Tsukada ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Advanced Stage ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Most patients with advanced-stage follicular lymphoma(FL) cannot be cured by conventional chemotherapy and have median survival of 7 to 10 years. High-dose chemotherapy (HDT) supported by autologous stem cell transplantation(ASCT) gives a survival benefit for patients with aggressive lymphoma. Recent several multicenter studies have shown that clinical and molecular remissions can be attained in patients with FL receiving intensified high-dose sequential chemotherapy and autografting. We have reported the efficacy and safety of high-dose bi-weekly THP-COP with G-CSF support (HDBW-TCOPG) for non-Hodgkin’s lymphoma. Therefore, we performed a pilot clinical trial to evaluate the efficacy and toxicity of HDBW-TCOPG followed by HDT with ASCT as first-line therapy in patients with advanced-stage FL. Patients and methods: Between August 1998 and December 2003, 10 Japanese patients with previously untreated FL from whom informed consent was obtained were included in this single-center pilot study. Median age was 48 years. All patients had stage 3 or 4 disease, aaIPI LI 8 and HI 2. Histological subtypes of FL included grade 1 4; grade 2 4; grade 3a 2. HDBW-TCOPG consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 from day 1 to 5; lenograstim 2.0 mg/kg/day from day 3. Five patients who enrolled after rituximab was approved for indolent B-cell lymphoma in Japan received induction therapy combined HDBW-TCOPG with rituximab 375mg/m2 on day -2 (R-HDBW-TCOPG). Six cycles were administered at intervals of two weeks. PBSC were collected during the later cycles of HDBW-TCOPG or on the recovery of high-dose etoposide regimen (500mg/m2 for 3 days) administered after the completion of HDBW-TCOPG. Leukaphereses were performed until a minimum of 2.0x106/kg CD34+ cells had been collected. The conditioning regimen consisted of ranimustine 200mg/m2 on day-7 and -2; paraplatin 300mg/m2 on day -6, -5, -4, -3; etoposide 500mg/m2 on day −5, −4, −3; cytarabine 2.5 g/m2 every 12 hours on day −2, −1 (MCE-CA regimen) in 2 patients or cyclophosphamide 50mg/kg on day −2, −1 (MCEC regimen) in 8 patients. Results: Sufficient numbers of PBSC were collected in 5 of 7 patients mobilized with HDBW-TCOPG and in all 5 patients with high-dose etoposide. The median time to reach total number of leukocytes of 1.0 x109/l was nine days (range 8–11). All 10 patients who were in PR at the end of HDBW-TCOP(G) achieved CR post APBSCT. After a median follow up of 36.6 months (range 7–66 months) PFS and OS are 90% and 90%, respectively, for all patients. One patient developed secondary myeloid leukemia with t(3;21) and died at 35 months after APBSCT without signs of recurrence of lymphoma. Another patient who relapsed at 35 months after transplantation. IgH or BCL2 rearrangement was detected by PCR analysis prior to therapy in three patients and one of them still showed detectable disease after HDBW-TCOPG induction. However, all three patients demonstrated MRD negativity after HDT with ASCT. Conclusion: HDBW-TCOPG as induction therapy followed by HDT with ASCT is feasible for advanced-stage FL with acceptable toxicity, and this short term highly intensified therapy may induce cure of the disease by minimizing MRD, but longer follow up is needed to evaluate the impact on survival.

scholarly journals AUTOLOGOUS STEM CELL TRANSPLANTATION FOR AGGRESSIVE LYMPHOMAS

2012 ◽  
Vol 4 (1) ◽  
pp. e2012075 ◽  
Author(s):  
Giuseppe Visani ◽  
Paola Picardi ◽  
Patrizia Tosi ◽  
Alessandro Isidori
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

The role of high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in the treatment armamentarium of aggressive B- and T-cell non-Hodgkin lymphoma (NHL) is still a matter of debate. In the pre-Rituximab era, the PARMA study demonstrated the superiority of HDT/ASCT over conventional salvage chemotherapy in chemosensitive, relapsed patients. Subsequently, HDT/ASCT has become a standard approach for relapsed NHL. With the advent of Rituximab in the landscape of NHL, transplantation as part of first-line therapy has been challenged. However, no benefit in terms of disease-free or overall survival of HDT/ASCT over standard therapy was shown when Rituximab was added to both arms. Moreover, the superiority of HDT/ASCT over conventional salvage therapy in patients relapsing from first-line therapy including Rituximab was not confirmed. From these disappointing results, novel strategies, which can enhance the anti-lymphoma effect, at the same time reducing toxicity have been developed, with the aim of improving the outcome of HDT/ASCT in aggressive NHL.In T-cell lymphoma, few publications demonstrated that consolidation of complete remission with HDT/ASCT is safe and feasible. However, up to one-third of patients may never receive transplant, mostly due to progressive disease, and relapse still remains a major concern even after transplant.

PET/CT Before Autologous Stem Cell Transplantation Predicts Outcome In High-Risk, Relapsed Follicular Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4370-4370
Author(s):  
Marion Alcantara ◽  
Jehan Dupuis ◽  
Michel Meignan ◽  
Anne Julian ◽  
Stephanie Becker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Conditioning Regimen ◽  
Tumor Burden ◽  
Ct Scans ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Pet Ct ◽  
Group 3

Abstract Introduction First-line immunochemotherapy followed by two years of rituximab (R) maintenance is now the standard of care for high-tumor burden follicular lymphoma (FL). In spite of an old controversy regarding the heterogeneous metabolic activity of FL lesions, either interim or final PET-CT after R-CHOP first-line therapy is now recognize to be strongly predictive of outcome. At the time of relapse, R-chemotherapy and autologous stem cell transplantation (ASCT) is a recommended option. Though, some patients will relapse quickly while others achieve long-term remissions. We investigated the prognostic value of PET-CT in patients with high-tumor burden relapsed FL treated with salvage R-chemotherapy followed by ASCT. Patients and Methods Seventy-five patients with relapsed FL referred to three French institutions were retrospectively analyzed. Patients with grade 3b follicular lymphoma or transformed into diffuse large B-cell lymphoma were excluded. Patients received second-line immunochemotherapy according to the local physician’s choice. We classified these salvage treatments into three groups: fludarabine-based regimen (n=29, group 1), cytarabine-based regimen (n=31, group 2), or ifosfamide-based regimen (n=15, group 3). PET-CT scans performed after salvage therapy (before ASCT) were included in the analyses. The local investigator’s interpretation of the imaging physician’s scan report defined a positive or negative PET. Results Median age was 56 years and 60% were men. Sixty eight patients received ASCT. Among this whole high-risk study population, 87% relapsed before 36 months after R-CHOP and 42% relapsed within 6 months and were therefore considered as R-CHOP refractory, with a median progression free survival (PFS) after R-CHOP first-line therapy of 15 months. Only 21% of the patients received R maintenance after R-CHOP. PET-CT scans after salvage therapy (before ASCT) were considered negative in 57%/76%/47% among the 3 groups respectively (p=0.06). Median stem cell harvest was higher in group 3-ifosfamide-based (8.3.106) than in both fludarabine and cytarabine-based regimens (4.47 and 4.8.106 respectively, Mann-Whitney p=0.15). Conditioning regimen was BEAM (37%) or Zevalin-BEAM (56%). Thirteen patients received R maintenance after ASCT. At a median follow-up of 28 months, 26/75 patients relapsed and 62 are alive. At 2 years, median PFS was 63.8%/66%/53.5% and median overall survival (OS) 68%/94%/92% among the 3 groups, respectively. PFS was only correlated to PET-CT results (p=0.0006). OS was correlated to group of therapy (2-3 versus 1), FLIPI score at relapse and PET-CT negativity. The latter was the strongest OS predictor on a multivariate analysis (p<0.01). On the other hand, age, gender, conditioning regimen, and PFS after R-CHOP (<36 months or even <12 months) were not linked to shorter PFS/OS. We observed 12% of second non-hematologic cancer. Conclusion PET-CT scan negativity after salvage treatment is the most important favourable factor for relapsed/refractory FL patients who receive ASCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals First-line therapy, autologous stem-cell transplantation, and post-transplantation maintenance in the management of newly diagnosed mantle cell lymphoma

2020 ◽  
Vol 27 (6) ◽  
Author(s):  
S. Bhella ◽  
N.P. Varela ◽  
A. Aw ◽  
C. Bredeson ◽  
M. Cheung ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Guidance Document ◽  
Newly Diagnosed ◽  
First Line ◽  
Post Transplantation ◽  
First Line Therapy ◽  
Line Therapy

Background In Ontario, no clearly defined standard of care for the management of mantle cell lymphoma (mcl) has been developed, and substantial variability from centre to centre is evident. This guidance document was prompted by the need to harmonize practice in Ontario with respect to first-line, conditioning, and post transplantation maintenance therapy for patients newly diagnosed with transplantation-eligible mcl. Methods The medline and embase databases were systematically searched from January 2013 to January 2020 for evidence, and the best available evidence was used to draft recommendations relevant to first-line therapy, autologous stem-cell transplantation, and post-transplantation maintenance in the management of transplantation-eligible newly diagnosed mcl. Final approval of this guidance document was obtained from the Stem Cell Transplant Advisory Committee. Recommendations These recommendations apply to all cases of transplantation-eligible newly diagnosed mcl:■ Alternating cycles of r-chop (rituximab plus cyclophosphamide–doxorubicin–vincristine–prednisolone) andr-dhap [rituximab plus dexamethasone–high-dose cytarabine–cisplatin] is the recommended first-line treatmentfor symptomatic patients newly diagnosed with mcl before autologous stem-cell transplantation (asct).■ Rituximab plus hyperfractionated cyclophosphamide–vincristine–doxorubicin–dexamethasone (r–hypercvad),alternating with methotrexate and cytarabine, is not recommended for the treatment of patients with newlydiagnosed mcl.■ beam (carmustine–etoposide–cytarabine–melphalan), beac (carmustine–etoposide–cytarabine–cyclophosphamide),and total-body irradiation–based regimens are reasonable conditioning options for patients with mcl whohave responded to first-line therapy and who are undergoing asct.■ Maintenance therapy with rituximab is recommended for patients with newly diagnosed mcl who have undergoneasct.

First-line Therapy With Donor-derived Human Cytomegalovirus (HCMV)–specific T Cells Reduces Persistent HCMV Infection by Promoting Antiviral Immunity After Allogenic Stem Cell Transplantation

2019 ◽  
Vol 70 (7) ◽  
pp. 1429-1437 ◽  
Author(s):  
Xiang-Yu Zhao ◽  
Xu-Ying Pei ◽  
Ying-Jun Chang ◽  
Xing-Xing Yu ◽  
Lan-Ping Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
First Line ◽  
Allogenic Stem Cell Transplantation ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Human cytomegalovirus (HCMV) infection, especially persistent HCMV infection, is an important cause of morbidity and mortality after allogenic stem cell transplantation (allo-SCT). Antiviral agents remain the first-line therapy but are limited by side effects and acquired resistance. Methods We evaluated the safety and efficacy of donor-derived HCMV-specific cytotoxic T cells (CTLs) as a first-line therapy for HCMV infection after allo-SCT and investigated the underlying mechanisms. Results In humanized HCMV-infected mice, first-line therapy with CTLs effectively combated systemic HCMV infection by promoting the restoration of graft-derived endogenous HCMV-specific immunity in vivo. In a clinical trial, compared with the pair-matched, high-risk control cohort, first-line therapy with CTLs significantly reduced the rate of persistent (2.9% vs 20.0%, P = .018) and late (5.7% vs 20.0%, P = .01) HCMV infection and cumulative incidence of persistent HCMV infection (hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.10–0.82; P = .02), lowered 1-year treatment-related mortality (HR, 0.15. 95% CI, 0.11–0.90. P = .03), and improved 1-year overall survival (HR, 6.35; 95% CI, 1.05–9.00; P = .04). Moreover, first-line therapy with CTLs promoted the quantitative and functional recovery of CTLs in patients, which was associated with HCMV clearance. Conclusions We provide robust support for the benefits of CTLs combined with antiviral drugs as a first-line therapy for treating HCMV infection and suggest that adoptively infused CTLs may stimulate the recovery of endogenous HCMV-specific immunity. Clinical trials registration NCT02985775.

Reduced Intensity Stem Cell Transplantation and Donor Lymphocyte Infusion after Imatinib Induction To Eradicate Residual Disease in Chronic Myeloid Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1097-1097
Author(s):  
Nicholas Heaney ◽  
Mhairi Copland ◽  
Karen Stewart ◽  
Judith Godden ◽  
Anne Parker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Control ◽  
Cell Transplantation ◽  
Residual Disease ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Reduced Intensity

Abstract Recommended first-line therapy for patients with chronic phase (CP) CML is imatinib mesylate (IM). Although IM induces complete cytogenetic responses (CCR) in the majority of patients, disease often remains detectable by Q-RT-PCR, likely reflecting stem cell persistence. Furthermore, primary and acquired resistance to IM have led to concerns about response durability. Allogeneic stem cell transplantation (SCT) remains the only curative option and with reduced intensity conditioning (RISCT) is less toxic and may be offered to a broader patient group. Our novel approach used IM to establish disease control (CCR) in patients with newly diagnosed CP CML prior to RISCT (fludarabine/melphalan/MabCampath). Prophylactic escalating DLI was given for residual disease. 18 patients (4 centres) were recruited between 2001 and 2006. Of these, 3 received myeloablative SCT, 2 for progression to blast crisis prior to SCT and the third for failing to reach a major cytogenetic response. 15 patients with a median age of 39y (21–56y) received sibling RISCT. Hasford scores were 38% low, 54% intermediate and 8% high risk. EBMT risk scores were 1–2 (13 patients) and 3–4 (2 patients). 5 patients required IM dose escalation to achieve CCR prior to RISCT. Follow-up data extends to a median of 31 (12–61) months (m) post RISCT. The RISCT procedure was well tolerated with rapid engraftment and short in-patient stays. 53% had infective episodes post RISCT, including CMV reactivation (86% patients at risk), EBV+ post transplant lymphoproliferative disease (2 patients) and PCP (1 patient). 1 patient developed aGvHD (grade III) and 8 cGvHD (6 limited, 2 extensive). DLI was given to 13 patients (87%), 6 for elevated Bcr-Abl, 4 for mixed chimerism and 2 for both. The median total dose was 0.65 × 107CD3+cells/kg (0.1–6.65 × 107cells/kg) in a median of 2 infusions. GvHD was seen in 6 of 12 patients receiving DLI (50%). IM was required in 4 patients with residual disease and all discontinued IM once disease control was re-established (4–13m of IM). 1 of 15 transplanted has died (at 12m with GvHD and infection). Of surviving patients median Bcr-Abl measurements fell as follow-up progressed. 8 patients currently have sustained undetectable Bcr-Abl. 7 of these 8 received DLI, the other had GvHD. The interval between last DLI and first proof of disease eradication was median 2m (range 1–28m). Only 2 of these 8 patients received IM post-transplant. In this study, the patients receiving RISCT were in early CP with a CCR to IM. It is likely that the majority would have maintained CCR if not offered transplantation. However the number of patients who achieved undetectable Bcr-Abl following RISCT and DLI compares favourably with the response expected with IM alone. The patients have tolerated the transplant procedure well and are currently off all treatment for CML. Regular monitoring remains necessary, however if relapse occurs it should be DLI responsive. Currently IM is the accepted first line therapy in the majority of patients however we would highlight the importance of RISCT in selected groups and believe our approach is effective and well tolerated.

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