Sequential therapy with alternating short courses of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R‐FM (rituximab, fludarabine, mitoxantrone) followed by autologous stem cell transplantation results in long term remission in advanced follicular lymphoma

Derenzini, Enrico; Casadei, Beatrice; Broccoli, Alessandro; Gandolfi, Letizia; Pellegrini, Cinzia; Zinzani, Pier Luigi

doi:10.1111/bjh.12894

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…The most relevant prognostic variable in our series was disease status at HDT/ASCT, a well-established factor [2,3,26,29,30]. Although the strategy of HDT/ASCT consolidation in CR1 has been used frequently in the past [23], it is currently less common owing to the emergence of new treatment options and drugs [31,32].…”

Section: Discussionmentioning

confidence: 93%

Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure

Jiménez‐Ubieto

Grande

Caballero

et al. 2017

Biology of Blood and Marrow Transplantation

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High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease (P < .001). In patients who received rituximab before ASCT, the estimated 9-year PFS and OS from ASCT were 59.5% (95% CI, 51%-67%) and 75% (95% CI, 68%-83%), respectively. Interestingly, for patients who underwent transplantation in CR ≥2 or PR ≥2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is of especial interest in pretransplantation rituximab-sensitive patients with FL.

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Section: Discussionmentioning

confidence: 93%

Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure

Jiménez‐Ubieto

Grande

Caballero

et al. 2017

Biology of Blood and Marrow Transplantation

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“…Some single studies have shown a better disease control in AHSCT arm, but it did not translate into better OS [19]. It may be partially due to an increased risk of secondary cancers after autograft [16]; however, this presumption has not been shown by others [20], including us. It was concluded that radiotherapy as a preparative regimen before AHSCT might be responsible for the development of secondary malignancies and should be avoided [12].…”

Section: Discussionmentioning

confidence: 92%

Autologous hematopoietic stem cell transplantation for relapsed follicular lymphoma: safety profile and clinical outcome in a single-center experience

et al. 2014

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Autologous hematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsed and recurrent follicular lymphoma (R/R FL); however, its value in the rituximab era remains to be elucidated. To evaluate the safety and clinical outcome of AHSCT for relapsed FL, we present a retrospective series of AHSCT for 30 FL patients (17 male and 13 female) at median age of 49 years. Patients were transplanted in second or subsequent complete or partial response after at least one therapeutic line including chemotherapy and rituximab. Overall, seven patients achieved second or higher complete response (CR) at AHSCT, whereas 23 were transplanted in partial response. Median overall survival (OS) was not reached, whereas progression-free survival (PFS) was 4.8 years. The estimated 10-year OS and PFS were found to be 60 and 33 %, respectively. There was no significant difference in OS and PFS in terms of FLIPI score and disease status at transplant. Median follow-ups from diagnosis and from AHSCT were 4.9 years (range 1.5–18.4 years) and 1.7 years (range 0.03–16.5 years), respectively. Fifteen patients relapsed, and 11 out of them (73 %) died of disease recurrence and chemoresistance. At the last contact, 19 patients are alive: 12 are in CR, whereas seven patients receive salvage regimens due to active lymphoma. AHSCT for relapsed FL patients who were pretreated with rituximab remains a safe procedure with low transplant-related mortality and long-term progression-free survival in about one-third of transplanted patients.

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In vitro and in vivo antineoplastic and immunological effects of pterocarpanquinone LQB-118

et al. 2016

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Cancer is a malignancy of worldwide prevalence, and although new therapeutic strategies are under investigation, patients still resort to reductive or palliative chemotherapy. Side effects are a great concern, since treatment can render patients susceptible to infections or secondary cancers. Thus, design of safer chemotherapeutic drugs must consider the risk of immunotoxicity. Pterocarpans are natural isoflavones that possess immunomodulatory and antineoplastic properties. Ubiquitous in nature, quinones are present in chemotherapeutic drugs such as doxorubicin and mitoxantrone. Our group has patented a hybrid molecule, the pterocarpanquinone LQB-118, and demonstrated its antineoplastic effect in vitro. In this report we describe its antineoplastic effect in vivo and assess its toxicity toward the immune system. Treated mice presented no changes in weight of primary and secondary organs of the immune system nor their cellular composition. Immunophenotyping showed that treatment increased CD4(+) thymocytes and proportionally reduced the CD4(+)CD8(+) subpopulation in the thymus. No significant changes were observed in T CD8(+) peripheral lymphocytes nor was the activation of fresh T cells affected after treatment. LQB-118 induced apoptosis in murine tumor cells in vitro, being synergistic with the autophagy promoter rapamycin. Furthermore, treatment significantly reduced ascites or solid Ehrlich and B16F10 melanoma growth in vivo, and ameliorated side effects such as cachexia. Based on its favorable preclinical profile and considering previous results obtained in vitro, this drug emerges as a promising candidate for further development.

show abstract

Sequential therapy with alternating short courses of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R‐FM (rituximab, fludarabine, mitoxantrone) followed by autologous stem cell transplantation results in long term remission in advanced follicular lymphoma

Cited by 3 publications

References 11 publications

Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure

Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure

Autologous hematopoietic stem cell transplantation for relapsed follicular lymphoma: safety profile and clinical outcome in a single-center experience

In vitro and in vivo antineoplastic and immunological effects of pterocarpanquinone LQB-118

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