Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex

Rowe, Jacob M.; Rapoport, Aaron P.; Ryan, Daniel; Nilsson, Bo; Duerst, R.; Packman, Charles H.; Abboud, Camille N.; DiPersio, John F.; Linder, Tammy; Wang, N.; Simonsson, Bengt; Liesveld, Jane L.

doi:10.1038/sj.bmt.1702037

Cited by 13 publications

(3 citation statements)

References 37 publications

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“…The histopathology of allogeneic cutaneous GVHD typically includes basal vacuolopathy and degeneration with or without lymphocytic infiltration, but eccrine gland involvement and destruction (as observed in the skin biopsy from one of our study patients) has also been reported especially in the chronic phase of allogeneic GHVD (47). A pattern of eccrine gland GVHD was described previously in patients who received an autologous transplant for CML followed by linomide, an immunomodulatory agent (48). …”

Section: Discussionmentioning

confidence: 78%

Rapid Immune Recovery and Graft-versus-Host Disease–like Engraftment Syndrome following Adoptive Transfer of Costimulated Autologous T Cells

Rapoport

Stadtmauer

Aqui

et al. 2009

Clinical Cancer Research

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Purpose: Previously, we showed that adoptive transfer of in vivo vaccine-primed and ex vivo (anti-CD3/anti-CD28) costimulated autologous T cells (ex-T) at day +12 after transplant increased CD4 and CD8 T-cell counts at day +42 and augmented vaccine-specific immune responses in patients with myeloma. Here, we investigated the safety and kinetics of T-cell recovery after infusing ex-Tat day +2 after transplant. Experimental Design: In this phase I/II two-arm clinical trial, 50 patients with myeloma received autografts after high-dose melphalan followed by infusions of ex-T at day +2 after transplant. Patients also received pretransplant and posttransplant immunizations using a pneumococcal conjugate vaccine only (arm B; n = 24) or the pneumococcal conjugate vaccine plus an HLA-A2^restricted multipeptide vaccine for HLA-A2 + patients (arm A; n = 26).

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Section: Discussionmentioning

confidence: 78%

Rapid Immune Recovery and Graft-versus-Host Disease–like Engraftment Syndrome following Adoptive Transfer of Costimulated Autologous T Cells

Rapoport

Stadtmauer

Aqui

et al. 2009

Clinical Cancer Research

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“…12 In another study, one patient (of 17) who received roquinimex as post transplant immunotherapy was PCR negative at 33 months of follow-up. 35 Although two of the molecular responses seen in our study occurred early after T-cell infusion and could have been due to the transplant alone, the response which occurred in patient UN-2 was delayed in onset and has been durable features which are more typical of an 'antileukemic' immune-mediated response. Although low-dose interferon alpha was utilized for maintenance therapy, in this patient, the disease was previously refractory to this agent.…”

Section: Discussionmentioning

confidence: 86%

Molecular remission of CML after autotransplantation followed by adoptive transfer of costimulated autologous T cells

Rapoport

Levine

Badros

et al. 2003

Bone Marrow Transplant

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Summary:Four patients with chronic myelogenous leukemia (CML) that was refractory to interferon alpha (two patients) or imatinib mesylate (two patients), and who lacked donors for allogeneic stem cell transplantation, received autotransplants followed by infusions of ex vivo costimulated autologous T cells. At day þ 30 (about 14 days after Tcell infusion), the mean CD4 þ cell count was 481 cells/ll (range 270-834) and the mean CD8 þ count was 516 cells/ll (range 173-1261). One patient had a relative lymphocytosis at 3.5 months after T-cell infusion, with CD4 and CD8 levels of 750 and 1985 cells/ll, respectively. All the four patients had complete cytogenetic remissions early after transplantation, three of whom also became PCR negative for the bcr/abl fusion mRNA. One patient, who had experienced progressive CML while on interferon alpha therapy, became PCRÀ post transplant, and remained in a molecular CR at 3.0 years of follow-up. All the four patients survived at 6, 9, 40, and 44 months post transplant; the patient who remained PCR þ had a cytogenetic and hematologic relapse of CML, but entered a molecular remission on imatinib. Autotransplantation followed by costimulated autologous T cells is feasible for patients with chronic phase CML, who lack allogeneic donors and can be associated with molecular remissions.

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“…Additionally, the NK cell line NK-92 was generated under good manufacturing practices with the purpose of ex vivo purging of CML cells for autografts due to its selective ability to lyse leukemic progenitors [51]. In terms of in vivo administration of activated NK cells, to our knowledge no studies have been conducted in CML patients, however use of NK stimulating agents such as IL-2 [52,53], and roquinimex [54], has been performed with some clinical benefit, although at present these therapies have not been optimized. Despite this, the clinical relevance of NK cells in CML should not be underestimated.…”

Section: Immunogenicity Of Cml: the Innate Immune Responsementioning

confidence: 99%

Therapeutic use of Aldara™ in chronic myeloid leukemia

Marleau¹,

Lipton

Riordan³

et al. 2007

J Transl Med

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The potent clinical responses seen in patients with chronic myeloid leukemia (CML) after administration of donor-specific lymphocytes, as well as the correlation between the presence of antigen specific T cells and prolonged remission in these patients, suggests a role for the immunological control of CML. Here we propose Aldara™, a clinically used formulation of imiquimod, as an agent for augmenting immune responses to CML antigens. Our proposition is based upon 3 tenets: 1) Endogenous dendritic cells (DC) of CML patients, which are known to be derived from the malignant clone, express and present various leukemic antigens; 2) CML-antigen reactive T cell clones exist in the patient but in many situations are ineffectively stimulated to cause significant hematological responses; and 3) Antigen presentation by mature, activated DC, which endogenously express CML-antigens may endow the pre-existing ineffective T cell responses with ability to control CML progression. The practical use of Aldara™ as a localized activator of DC in the context of present day leukemic therapeutics, as well as various properties of this unique immune modulator will be discussed.

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Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex

Cited by 13 publications

References 37 publications

Rapid Immune Recovery and Graft-versus-Host Disease–like Engraftment Syndrome following Adoptive Transfer of Costimulated Autologous T Cells

Rapid Immune Recovery and Graft-versus-Host Disease–like Engraftment Syndrome following Adoptive Transfer of Costimulated Autologous T Cells

Molecular remission of CML after autotransplantation followed by adoptive transfer of costimulated autologous T cells

Therapeutic use of Aldara™ in chronic myeloid leukemia

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