scholarly journals Clonal hematopoiesis evolves from pretreatment clones and stabilizes after end of chemotherapy in patients with MCL

Blood ◽  
2020 ◽  
Vol 135 (22) ◽  
pp. 2000-2004 ◽  
Author(s):  
Christian Winther Eskelund ◽  
Simon Husby ◽  
Francesco Favero ◽  
Tobias Wirenfeldt Klausen ◽  
Francisco German Rodriguez-Gonzalez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
First Line ◽  
Clonal Hematopoiesis ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mantle Cell ◽  
Good Risk ◽  
Line Chemotherapy

Eskelund et al examined clonal hematopoiesis (CH) in a cohort of patients with mantle cell lymphoma (MCL) treated with first-line chemotherapy and autologous stem cell transplantation. In young, good-risk MCL patients, CH after first-line therapy arises almost entirely from preexisting clones, stabilizes after a period of expansion posttransplantation, and does not negatively impact survival.

The EBMT Lymphoma Working Party-European Mantle Cell Lymphoma Network Consensus Project On The Role Of Autologous and Allogeneic Stem Cell Transplantation In Mantle Cell Lymphoma: Recommendations Applying The Delphi Procedure

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3405-3405 ◽  
Author(s):  
Stephen Paul Robinson ◽  
Paolo Corradini ◽  
Peter Dreger ◽  
Dolores Caballero ◽  
Christian H Geisler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mantle Cell

Abstract Introduction The role of both autologous (autoSCT) and allogeneic stem cell transplantation (alloSCT) in the management of patients with mantle cell lymphoma (MCL) remains to be clarified. In the absence of prospective comparative trials decision making for clinicians remains challenging. We have conducted a consensus project to provide guidance on how stem cell transplantation should be employed in MCL. Methods This was a collaborative project between the Lymphoma Working Party of the EBMT and the European Mantle Cell Lymphoma Network. The RAND modified Delphi consensus procedure was used. 12 clinicians, recognized for their expertise in MCL, from both transplant and non-transplant centres contributed. A literature search was performed and consensus statements were formulated. Panel members ranked each statement. The statements were reviewed and modified and then a second round of ranking was performed. Results Consensus agreement was reached on the following statements: 1. Patients should be considered for transplant strategies based on their biological age and comorbidities and not just chronological age. 2. An autoSCT should be considered as the standard first line consolidation therapy in all patients considered suitable for high dose therapy. 3. First line induction therapy prior to SCT should incorporate high dose cytarabine and Rituximab based regimens. 4. Patients achieving either complete remission or partial remission following induction therapy should be considered for autoSCT. 5. Patients failing to achieve a PR or CR following induction therapy should not proceed directly to an autoSCT. 6. Patients undergoing an allogeneic SCT should receive reduced intensity conditioning regimens. There was consensus disagreeing with the following statement: Prognostic criteria are available that permit the identification of low risk patients in need of first line therapy who should be considered for non-transplant based treatment. There was partial consensus agreeing with the following statements: 1. Patients relapsing after an autoSCT should be considered for an allogeneic stem cell transplant following reinduction therapy.2. Patients with evidence of MRD relapse post alloSCT should, in the absence of graft versus host disease, be considered for rapid withdrawal of immunesuppression and donor lymphocyte infusions. There was a partial consensus disagreeing with the following statements: 1 Patients should receive Rituximab maintenance following first line autologous stem cell transplant. 2. There are sufficient prognostic criteria to identify patients who should undergo an allogeneic stem cell transplantation as first line consolidation. 3. In patients relapsing after non-transplant first line therapy there are sufficient prognostic criteria to determine whether autoSCT or alloSCT consolidation should be used. Finally there was no consensus with respect to the following statements. 1. Disease response to induction therapy prior to autoSCT should be assessed by PET scan. 2. Minimal residual disease (MRD) negativity is mandatory prior to autoSCT. 3. A TBI based regimen should be considered as the standard for conditioning prior to autoSCT. 4. Patients undergoing an autoSCT should receive in-vivo purging with Rituximab at the time of high dose conditioning therapy. 5. Patients with relapsed disease following non-transplant first line therapy should be considered for an autologous stem cell transplant to consolidate second (or higher) response. 6. Patients with relapsed disease following non-transplant first line therapy should be considered for an allogeneic SCT to consolidate second (or higher) response. 7. Patients undergoing autoSCT should be monitored for MRD post transplant. 8. Patients with evidence of MRD relapse post autoSCT should receive preemptive Rituximab. 9. Patients undergoing alloSCT should be monitored for MRD post transplant. Conclusions Consensus was obtained with regard to the role of autologous SCT in first line consolidation. However, the application of appropriate clinical and molecular prognostic factors to guide therapeutic decisions and the role of allogeneic transplantation warrant further clinical investigation. Disclosures: No relevant conflicts of interest to declare.

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.

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.

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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