Specific Features Identify Patients with Relapsed or Refractory Mantle Cell Lymphoma Benefitting from Autologous Hematopoietic Cell Transplantation

Cassaday, Ryan D.; Guthrie, Katherine A.; Budde, Lihua E.; Thompson, Leslie; Till, Brian G.; Press, Oliver W.; Chauncey, Thomas R.; Pagel, John M.; Petersdorf, Stephen H.; Palanca-Wessels, Maria Corinna; Philip, Mary; Bensinger, William I.; Holmberg, Leona; Shustov, Andrei R.; Green, Damian J.; Libby, Edward N.; Maloney, David G.; Gopal, Ajay K.

doi:10.1016/j.bbmt.2013.07.005

Cited by 23 publications

(10 citation statements)

References 15 publications

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“…The remission quotient (RQ) – calculated by dividing the time (in months) from diagnosis to ASCT by the number of prior treatments was assessed. We developed the RQ as a prognostic marker in relapsed mantle cell lymphoma patients undergoing ASCT [6], with a score of less than 6 being particularly unfavorable. Although its utility in FL has not yet been established, we found the RQ useful to demonstrate the number of treatments received as a function of disease duration prior to ASCT because the timing of and need for treatment/transplant in FL varies widely among referral practices, treating physicians, and individual disease states.…”

Section: Methodsmentioning

confidence: 99%

Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity

Phipps

Gopal

Storer

et al. 2014

Leukemia & Lymphoma

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Rituximab-refractory follicular lymphoma (FL) patients have limited options. Before the rituximab era, autologous stem cell transplantation (ASCT) was shown to improve outcomes in chemotherapy-sensitive, relapsed FL, but the impact of rituximab-sensitivity on these results is unknown. We analyzed 194 consecutive relapsed FL patients who underwent ASCT at out center and categorized them as rituximab-sensitive (RS, n=35), rituximab-refractory (RR, n=65), or no rituximab (NoR, n=94) if transplanted before rituximab was used. Progression-free survival at 3 years was 85% in RS and 35% in RR patients (P = .0004). Only rituximab-sensitivity was significant on multivariate analysis with improved OS (HR 0.24, P = .01) and PFS (HR 0.35, P = .006) in RS patients and increased relapse in RR patients (HR 2.11, P = .01). Pre-transplant rituximab-sensitivity is a strong independent predictor of post-transplant outcomes in relapsed FL, though one-third of RR patients achieved a PFS of over 3 years with ASCT.

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Section: Methodsmentioning

confidence: 99%

Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity

Phipps

Gopal

Storer

et al. 2014

Leukemia & Lymphoma

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“…More recent studies, however, including a large retrospective study from the CIBMTR, indicated that durable remissions in the 2–4 year range may be observed for select MCL patients whose disease remains chemosensitive. [68,72] Therefore, in relapsed MCL patients with chemosensitive disease, who are not candidates for a potentially curative allogeneic-HCT (due to co-morbidities, donor availability etc. ), consolidation with an auto-HCT can be offered, with the understanding that this therapy is not curative.…”

Section: Mantle Cell Lymphoma (Mcl)mentioning

confidence: 99%

Allogeneic Hematopoietic Cell Transplantation as Curative Therapy for Patients with Non-Hodgkin Lymphoma: Increasingly Successful Application to Older Patients

Fenske

Hamadani

Cohen

et al. 2016

Biology of Blood and Marrow Transplantation

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Non-Hodgkin lymphoma (NHL) constitutes a collection of lymphoproliferative disorders with widely varying biologic, histologic and clinical features. For the B-cell NHLs, great progress has been made due to the addition of monoclonal antibodies and, more recently, other novel agents such as B-cell receptor signaling inhibitors, immunomodulatory agents, and proteasome inhibitors. Autologous hematopoietic cell transplantation (auto-HCT) offers the promise of cure or prolonged remission in some NHL patients. For some patients, however, auto-HCT may never be a viable option, while in others their disease may progress despite auto-HCT. In those settings, allogeneic HCT (allo-HCT) offers the potential for cure. Over the past 10–15 years, considerable progress has been made in the implementation of allo-HCT, such that this approach now is a highly effective therapy for patients up to (and even beyond) age 75. Recent advances in conventional lymphoma therapy, peri-transplant supportive care, patient selection, and donor selection (including the use of alternative hematopoietic cell donors), has allowed broader application of allo-HCT to NHL patients. As a result, an ever-increasing number of NHL patients over age 60–65 years stand to benefit from allo-HCT. In this review, we present data in support of the use of allo-HCT for patients with diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. These histologies account for a large majority of allo-HCT performed for patients over 60 in the U.S. Where possible, we highlight available data in older patients. This body of literature strongly supports the concept that allo-HCT should be offered to fit patients well beyond age 65 and, accordingly, that this treatment should therefore be covered by their insurance carriers.

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“…58,59 Recent data suggest that post-transplant cyclophosphamide administration primarily targets rapidly-dividing allo-specific cells, relatively sparing naïve cells essential to maintenance of immunocompetence following HSCT. 60 CD4 + Foxp3 + T regs appear resistant to cyclophosphamide and recover quickly following cyclophosphamide induction for allogeneic bone marrow transplantation. 61 Sparing of T regs may partly underlie the mechanism by which cyclophosphamide prevents GVHD.…”

Section: Clinical Implications For Autoimmunity After Treatment Omentioning

confidence: 99%

Homeostatic expansion as a barrier to lymphocyte depletion strategies

Zwang

Turka²

2014

Current Opinion in Organ Transplantation

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Introduction Purpose of review Following lymphodepletion, lymphocytes repopulate the immune space both through enhanced thymopoiesis and proliferation of residual non-depleted peripheral lymphocytes. The term homeostatic proliferation (alternatively homeostatic expansion or lymphopenia-induced proliferation) refers to the latter process. Homeostatic proliferation is especially relevant to reconstitution of the lymphocyte compartment following immunodepletion therapy in transplantation. Repopulating lymphocytes can skew toward an effector memory type capable of inducing graft rejection, autoimmunity, or, in the case of allogeneic bone marrow transplantation, graft versus host disease. Here we review recent studies exploring the biologic mechanisms underlying homeostatic proliferation and explore implications for therapy in transplantation. Recent findings Two immune-depleting agents, alemtuzumab and rabbit antithymocyte globulin, have been well-characterized in their abilities to induce an effector-memory phenotype in repopulating lymphocytes. Additionally, we have gained new understandings of the mechanisms by which the cytokines Interleukin-7 (IL-7) and Interleukin-15 (IL-15) regulate this process. Recent studies have also explored the functions of non-cytokine and signaling molecules in lymphopnenia-induced proliferation. Finally, we have seen the promise and limitations of several therapeutic approaches, including recombinant IL-7 therapy, CD8+-targeted antibodies, and peri-transplant cyclophosphamide, to treat post-transplant lymphopenia and reduce the risks of immune dysregulation following homeostatic proliferation. Summary Immune dysfunction following homeostatic proliferation is a special challenge in transplantation. A deeper understanding of the underlying biology has led to a number of promising new therapies to overcome this problem.

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Specific Features Identify Patients with Relapsed or Refractory Mantle Cell Lymphoma Benefitting from Autologous Hematopoietic Cell Transplantation

Cited by 23 publications

References 15 publications

Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity

Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity

Allogeneic Hematopoietic Cell Transplantation as Curative Therapy for Patients with Non-Hodgkin Lymphoma: Increasingly Successful Application to Older Patients

Homeostatic expansion as a barrier to lymphocyte depletion strategies

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