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1.
Age and lymphocyte/monocyte ratio as prognostic factors for autologous transplantation in the treatment of patients with follicular lymphoma
Kenyeres, A., Kiss, E., Simon, Z., Illés, Á, Jóna, Á
The Journal of international medical research. 2024;52(2):3000605231221012
Abstract
OBJECTIVE Follicular lymphoma (FL) is an indolent, lymphoproliferative disease of B-cell origin that has a heterogeneous disease course with varying outcomes. Certain patients may undergo autologous stem cell transplantation. We investigated the outcome of autologous stem cell transplantation in patients with FL. METHODS Patients who received autologous stem cell transplantation at the University of Debrecen's Department of Hematology between 2004 and 2021 were retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) after transplantation of patients with FL were examined. Prognostic factors that may influence the course of the disease were chosen. RESULTS Data were collected from 49 patients. OS was influenced only by age, whereas PFS was affected by age and the lymphocyte/monocyte ratio. The combination of age and lymphocyte/monocyte ratio defined a patient population with a particularly unfavorable prognostic risk profile: patients over 47 years of age with a pre-transplant lymphocyte/monocyte ratio greater than or equal to 2.675. CONCLUSION Age and lymphocyte/monocyte ratio were identified as useful prognostic factors for PFS in patients with FL following autologous stem cell transplantation.
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2.
Are dynamic or fixed FDG-PET measures of disease of greater prognostic value in patients with relapsed/refractory diffuse large B-cell lymphoma undergoing autologous haematopoietic stem cell transplantation?
Campbell, B. A., Brown, R., Lambertini, A., Hofman, M. S., Bressel, M., Seymour, J. F., Wirth, A., MacManus, M., Dickinson, M.
British journal of haematology. 2023
Abstract
Positron emission tomography (PET) response assessment using the Deauville score has prognostic utility in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem-cell transplantation (ASCT). Improved predictive methods are required to identify patients with poor outcomes who may be better considered for other salvage options. We investigated the prognostic value of mean tumour volume (MTV) and maximum standardised uptake value (SUVmax) at pre-salvage and pre-ASCT time-points, and the quantitative changes between scans (∆MTV and ∆SUVmax). One hundred and twenty-five patients with R/R DLBCL underwent salvage immunochemotherapy and ASCT 80 patients had pre-salvage PET and 90 had pre-ASCT PET available. With a median follow-up of 5.6 years, 5-year progression-free survival (PFS) and overall survival (OS) were 52% and 65%, respectively. For patients with PET-positive residual disease after salvage therapy, pre-ASCT MTV was a significant negative prognosticator for PFS (HR 1.19 per 100 ml, p < 0.001) and OS (HR 1.78 per 100 ml, p < 0.001). Similarly, pre-ASCT SUVmax was negatively associated with PFS (HR 1.08, p < 0.001) and OS (HR 1.08, p < 0.001). Notably, pre-salvage MTV and SUVmax and ∆MTV and ∆SUVmax were not associated with PFS or OS. In conclusion, pre-ASCT MTV and SUVmax appear to be of greater predictive value than the degree of response. Potential application may exist for PET-directed management of R/R DLBCL patients.
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3.
Allogeneic stem cell transplantation achieves long-term remissions in mantle cell lymphoma, including in TP53-mutated disease
Lew, T. E., Cliff, E. R. S., Dickinson, M., Tam, C. S., Seymour, J. F., Blombery, P., Bajel, A., Ritchie, D., Khot, A.
Leukemia & lymphoma. 2023;:1-9
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Full text
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Editor's Choice
Abstract
Cytarabine-containing chemoimmunotherapy followed by autologous transplantation and rituximab maintenance achieves durable remissions for most patients with mantle cell lymphoma (MCL). However, patients with TP53-mutated disease have poor outcomes with standard approaches. We previously reported that allogeneic stem cell transplantation (alloSCT) achieved durable remissions in MCL, however follow-up among patients with TP53-mutated disease was limited. Here we report extended follow-up of the overall cohort (n = 36) and TP53-mutated subset (n = 13) (median follow-up 10.8 and 4.2 years, respectively). Estimated overall survival was 56% at 10 years for the overall cohort and 59% at 4 years for the TP53-mutated subset. Among patients with TP53-mutated disease, no relapses occurred beyond 6 months post-transplant. Survival after post-alloSCT disease relapse was poor (median 2.1 years). These data confirm that alloSCT can be curative in MCL, including patients with TP53-mutated disease, and should be considered for earlier utilization in this subgroup for whom conventional chemoimmunotherapy is ineffective.
PICO Summary
Population
Retrospective cohort of adults who received allogeneic HSCT for mantle cell lymphoma and available for extended follow-up, from a single centre in Australia, (n=36)
Intervention
Allogeneic HSCT (TP53-mutated subset, n=13)
Comparison
Allogeneic HSCT (Overall cohort, n=36)
Outcome
Estimated overall survival was 56% at 10 years for the overall cohort and 59% at 4 years for the TP53-mutated subset. Among patients with TP53-mutated disease, no relapses occurred beyond 6 months post-transplant. Survival after post-alloSCT disease relapse was poor (median 2.1 years).
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Relapse Timing Is Associated With Distinct Evolutionary Dynamics in Diffuse Large B-Cell Lymphoma
Hilton, L. K., Ngu, H. S., Collinge, B., Dreval, K., Ben-Neriah, S., Rushton, C. K., Wong, J. C. H., Cruz, M., Roth, A., Boyle, M., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023;:Jco2300570
Abstract
PURPOSE Diffuse large B-cell lymphoma (DLBCL) is cured in more than 60% of patients, but outcomes remain poor for patients experiencing disease progression or relapse (refractory or relapsed DLBCL [rrDLBCL]), particularly if these events occur early. Although previous studies examining cohorts of rrDLBCL have identified features that are enriched at relapse, few have directly compared serial biopsies to uncover biological and evolutionary dynamics driving rrDLBCL. Here, we sought to confirm the relationship between relapse timing and outcomes after second-line (immuno)chemotherapy and determine the evolutionary dynamics that underpin that relationship. PATIENTS AND METHODS Outcomes were examined in a population-based cohort of 221 patients with DLBCL who experienced progression/relapse after frontline treatment and were treated with second-line (immuno)chemotherapy with an intention-to-treat with autologous stem-cell transplantation (ASCT). Serial DLBCL biopsies from a partially overlapping cohort of 129 patients underwent molecular characterization, including whole-genome or whole-exome sequencing in 73 patients. RESULTS Outcomes to second-line therapy and ASCT are superior for late relapse (>2 years postdiagnosis) versus primary refractory (<9 months) or early relapse (9-24 months). Diagnostic and relapse biopsies were mostly concordant for cell-of-origin classification and genetics-based subgroup. Despite this concordance, the number of mutations exclusive to each biopsy increased with time since diagnosis, and late relapses shared few mutations with their diagnostic counterpart, demonstrating a branching evolution pattern. In patients with highly divergent tumors, many of the same genes acquired new mutations independently in each tumor, suggesting that the earliest mutations in a shared precursor cell constrain tumor evolution toward the same genetics-based subgroups at both diagnosis and relapse. CONCLUSION These results suggest that late relapses commonly represent genetically distinct and chemotherapy-naïve disease and have implications for optimal patient management.
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5.
Clinical relevance of MYC/BCL2 expression and cell of origin in patients with diffuse large b-cell lymphoma treated with autologous transplant
Al-Juhaishi, T., Wang, Y., Milton, D. R., Xu-Monette, Z. Y., Jabbour, E., Daher, M., Im, J. S., Bashir, Q., Iyer, S. P., Marin, D., et al
Bone marrow transplantation. 2023
Abstract
Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall survival. On multivariable analysis, DEL/DHL, age >60 years, and >2 prior therapies, but not COO, were important prognostic factors for overall survival. When we explored the interaction of COO and BCL2 expression, patients with germinal center B-cell (GCB)/BCL2 (+) had inferior progression-free survival (PFS) compared to GCB/BCL2 (-) patients (HR, 4.97; P = 0.027). We conclude that the DEL/non-DHL and non-DEL/non-DHL subtypes of DLBCL have similar survival after ASCT. The negative impact of GCB/BCL2 (+) on PFS warrants future trials targeting BCL2 after ASCT. The inferior outcomes in DEL/DHL need to be verified in a larger number of patients.
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Long-term outcome in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation
Metzner, B., Müller, T. H., Casper, J., Kimmich, C., Köhne, C. H., Petershofen, E., Renzelmann, A., Thole, R., Voss, A., Dreyling, M., et al
European journal of haematology. 2023
Abstract
BACKGROUND Long-term clinical and molecular remissions in patients with mantle cell lymphoma (MCL) after autologous stem cell transplantation (ASCT) have been evaluated in only a few studies. DESIGN AND METHODS Sixty-five patients with MCL received ASCT (54 first-line ASCT, 10 second-line ASCT, and 1 third-line ASCT). In the case of long-term remission (≥5 years; n = 27), peripheral blood was tested for minimal residual disease (MRD) by t(11;14)- and IGH-PCR at the last follow-up. RESULTS Ten-year overall survival (OS), progression-free survival (PFS), and freedom from progression (FFP) after first-line ASCT were 64%, 52%, and 59% versus after second-line ASCT 50%, 20%, and 20%, respectively. Five-year OS, PFS, and FFP for the first-line cohort were 79%, 63%, and 69%, respectively. Five-year OS, PFS, and FFP after second-line ASCT were 60%, 30%, and 30%, respectively. Treatment-related mortality (3 months after ASCT) was 1.5%. So far 26 patients developed sustained long-term clinical and molecular complete remissions of up to 19 years following ASCT in first treatment line. CONCLUSION Sustained long-term clinical and molecular remissions are achievable following ASCT.
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[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma]
Luo, L., Jiao, Y., Yang, P., Li, Y., Huang, W. Y., Ke, X. Y., Zou, D. H., Jing, H. M.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2023;44(5):388-394
Abstract
Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.
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8.
Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406
Ogura, M., Yamamoto, K., Morishima, Y., Wakabayashi, M., Tobinai, K., Ando, K., Uike, N., Kurosawa, M., Gomyo, H., Taniwaki, M., et al
Cancer science. 2023
Abstract
Progression-free survival after R-High CHOP/CHASER/LEED with auto-PBSCT in untreated mantle cell lymphoma in JCOG0406 study. A continuous pattern of relapse was observed.
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9.
The association of body composition and outcomes following autologous hematopoietic stem cell transplantation in patients with non-Hodgkin lymphoma
Aleixo, G. F. P., Wei, W., Chen, P. H., Gandhi, N. S., Anwer, F., Dean, R., Hamilton, B. K., Hill, B. T., Jagadeesh, D., Khouri, J., et al
Bone marrow transplantation. 2023
Abstract
Recently there has been a growing interest in evaluating body composition as a marker for prognosis in cancer patients. The association of body composition parameters and outcomes has not been deeply investigated in patients with autologous hematopoietic stem cell transplantation (HSCT) recipients with non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of 264 NHL patients who received autologous HSCT. PreHSCT abdominal CT scans at the levels of L3 were assessed for body composition measures. We evaluated sarcopenia, myosteatosis, high visceral adipose tissue (VAT) and high visceral adipose tissue density (VATD). Using multivariable Cox proportional regression, we analyzed the association of clinical and transplant-related characteristics with overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM). In a multivariate regression model, patients with higher VATD had worse OS (HR 1.78; 95% confidence intervals CI 1.08-2.95, p = 0.02) and worse NRM (HR 2.31 95% CI 1.08-4.95, p = 0.02) than with lower VATD. Patients with lower levels of VAT also had worse RFS (HR 1.49 95% CI 1.03-2.15, p = 0.03). Sarcopenia and myosteatosis were not associated with outcomes. High pre-transplant VATD was associated with lower OS and higher NRM, and low pre-transplant VAT was associated with worse RFS in patients with NHL undergoing autologous HSCT.
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10.
Humoral immune-depression following autologous stem cell transplantation is a marker of prolonged response duration in patients with mantle cell lymphoma
Bouard, L., Tessoulin, B., Thieblemont, C., Bouabdallah, K., Gastinne, T., Oberic, L., Carras, S., Delette, C., Casasnovas, O., Dartigeas, C., et al
Haematologica. 2022
Abstract
Rituximab maintenance (RM) after autologous stem cell transplantation (ASCT) is standardof-care for young patients with mantle cell lymphoma (MCL). RM may enhance posttransplantation immune-depression and risk of infections. We compared infection incidence and immune consequences of RM versus observation in transplanted MCL patients. All randomized patients included in the LyMa trial were eligible. The following parameters were collected prospectively: occurrence of fever, infection, hospitalization, neutropenia, hypogammaglobulinemia, CD4 lymphopenia and gamma globulin (Ig) substitution. The post-ASCT period was divided into 4 periods in order to assess the possible effects of RM or ASCT on immune status. Each arm included 120 patients. Concerning infection incidence and all biological parameters, there was no difference between the 2 arms during the first year post-ASCT. After this period, RM patients were more exposed to fever (p=0.03), infections (p=0.001), hypogammaglobulinemia (p=0.0001) and Ig substitution (p.