Phase II Study of Recombinant Human Interferon Gamma for Treatment of Cutaneous T-Cell Lymphoma

Kaplan, Edward H.; Rosen, Steven T.; Norris, David B.; Roenigk, Henry H.; Saks, Samuel; Bunn, Paul A.

doi:10.1093/jnci/82.3.208

Cited by 158 publications

(74 citation statements)

References 11 publications

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“…A number of systemic cytokines such as interferon gamma, interleukin-2 and interleukin-12 act through immune mechanisms and have been reported to have anti-MF activity. [13][14][15][16][17] To our knowledge, this is the first reported evidence for an allogeneic graft-versus-mycosis fungoides effect.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides: evidence of a graft-versus-tumor effect

Burt

Guitart

Traynor

et al. 2000

Bone Marrow Transplant

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Summary:Allogeneic hematopoietic stem cell transplantation should be considered as a therapeutic option for patients with generalized erythoderma or tumor stage MF. Indeed, the only curative option for MF may be an allogeneic transplant. Bone Marrow Transplantation (2000) 25, 111-113. Keywords: allogeneic hematopoietic stem cell transplant; mycosis fungoides; cutaneous T cell lymphoma Mycosis fungoides (MF) is a low-grade lymphoma that primarily manifests as cutaneous plaques or tumors. 1,2 Progression is accompanied by spread to lymph nodes and visceral organs. Histopathology reveals an epidermotropic lymphocytic infiltrate composed of atypical lymphocytes. 3 The atypical cells may also be seen in the peripheral blood and are characterized by their cerebriform or hyperconvoluted nuclear detail. MF cells are of the T cell lineage and usually have a CD4 ϩ CD45RO ϩ memory-helper phenotype. 4 The natural history of MF is usually indolent. Over many years MF may evolve from premalignant cutaneous lesions and scaly erythematous patches into palpable plaques and finally tumors. The mean survival for patients with early patch lesions may exceed 10-15 years. However, patients with generalized erythroderma or tumor at the time of presentation have a poorer prognosis with a median survival of 2-4 years. Early stage lesions are treated with psoralen and ultraviolet light A (PUVA), topical chemotherapy, extracorporeal photophoresis, interferon, and/or electron beam irradiation. 5,6 Advanced disease is treated with interferon, retinoids or combination chemotherapy regimens, with mixed results. 5,7 To our knowledge, we report the first case of reinduction of clinical and histologic remission following withdrawal of immunosuppressive medication after allogeneic hematopoietic stem cell transplantation, providing evidence for an immunologic graft-versus-MF effect. Case reportA 27-year-old black woman was diagnosed with mycosis fungoides (stage T3 N1 M0). She had failed multiple prior therapies including PUVA, PUVA and interferon, six cycles of CHOP (cyclophosphamide, adriamycin, vincristine, prednisone), and two cycles of 9-aminocamptothecin. The patient's skin was diffusely infiltrated with patches, plaques and tumors. Lymphatic and visceral organs were involved. An allogeneic HLA matched sibling transplant was performed using an unmanipulated marrow and CD34 immunoselected blood graft. Conditioning was with cyclophosphamide (200 mg/kg) and total body irradiation (1200 cGy). The post-transplant course was complicated by acute graft-versus-host disease (grade II) that resolved on corticosteroid and cyclosporine immunosuppressive therapy.The patient remained in complete remission for 9 months when new plaques were noted over the right thigh and chest (Figure 1a). Relapse of MF was confirmed by skin biopsy (Figure 1b and c). Since there was no clinical evidence of GVHD, prophylactic immunosuppression with cyclosporine was discontinued. Within 1 month, the plaques resolved and were replaced by flat and scaly hypopigmented patches....

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Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides: evidence of a graft-versus-tumor effect

Burt

Guitart

Traynor

et al. 2000

Bone Marrow Transplant

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“…Prolonged responses have also been observed with ␥-interferon. 56 Recombinant interleukin-12 (IL-12) has efficacy in MF, but limited availability does not make it a realistic treatment option at present. 57…”

Section: Ifn-␣ and Related Biologic Response Modifiersmentioning

confidence: 99%

How I treat mycosis fungoides and Sézary syndrome

Prince

Whittaker

Hoppe

2009

Blood

136

109

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The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a “stage-based” approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-α, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.

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“…There is also evidence that cytokines may rise as a consequence of the cancer therapy itself. Cachexia-like symptoms have been reported as common side effects of IFN therapy in cancer patients (59), and elevated IFN levels were also reported in patients receiving IL-2 and IFN-β therapy (60). We envision that regulation of myosin at the RNA level may be a contributing mechanism to muscle breakdown in conditions that favor persistent signaling from both TNF and IFN.…”

Section: Figurementioning

confidence: 99%

Cancer cachexia is regulated by selective targeting of skeletal muscle gene products

Acharyya

Ladner²,

Nelsen³

et al. 2004

J. Clin. Invest.

277

215

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Cachexia is a syndrome characterized by wasting of skeletal muscle and contributes to nearly one-third of all cancer deaths. Cytokines and tumor factors mediate wasting by suppressing muscle gene products, but exactly which products are targeted by these cachectic factors is not well understood. Because of their functional relevance to muscle architecture, such targets are presumed to represent myofibrillar proteins, but whether these proteins are regulated in a general or a selective manner is also unclear. Here we demonstrate, using in vitro and in vivo models of muscle wasting, that cachectic factors are remarkably selective in targeting myosin heavy chain. In myotubes and mouse muscles, TNF-α plus IFN-γ strongly reduced myosin expression through an RNA-dependent mechanism. Likewise, colon-26 tumors in mice caused the selective reduction of this myofibrillar protein, and this reduction correlated with wasting. Under these conditions, however, loss of myosin was associated with the ubiquitin-dependent proteasome pathway, which suggests that mechanisms used to regulate the expression of muscle proteins may be cachectic factor specific. These results shed new light on cancer cachexia by revealing that wasting does not result from a general downregulation of muscle proteins but rather is highly selective as to which proteins are targeted during the wasting state.

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Phase II Study of Recombinant Human Interferon Gamma for Treatment of Cutaneous T-Cell Lymphoma

Cited by 158 publications

References 11 publications

Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides: evidence of a graft-versus-tumor effect

Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides: evidence of a graft-versus-tumor effect

How I treat mycosis fungoides and Sézary syndrome

Cancer cachexia is regulated by selective targeting of skeletal muscle gene products

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