Efficacy of recombinant interferon‐alpha (rIFN‐α) in polycythaemia vera: a study of 17 patients and an analysis of published data

Taylor, P C; Dolan, G.; Ng, Johan Y. Y.; Paul, Beverley; Collin, R; Reilly, J

doi:10.1046/j.1365-2141.1996.00303.x

Cited by 43 publications

(27 citation statements)

References 18 publications

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“…Extracted data from the published results of 100 patients with PV who were treated with rIFN-· show that 60% achieved CR, 27% PR, 13% NR and 77% had a 50% reduction in pruritus complaints [9]. This study is another confirmation of these data showing rIFN-· to be an effective agent in the treatment of myeloproliferation in PV (Hb and platelet counts, spleen size, phlebotomy requirements).…”

Section: Discussionsupporting

confidence: 66%

“…Haematological responses were defined as follows: complete response (CR) Hct ! 45% in the absence of phlebotomy, partial response (PR) a 50% reduction of phlebotomy requirements with a Hct of 45-50% and the remainder were considered as no response (NR) [9].…”

Section: Methodsmentioning

confidence: 99%

“…Recently, rIFN-· has been reported to induce complete or partial haematological responses and to improve PV-associated pruritus in a limited number of patients [9][10][11][12][13]. In the light of these data we investigated the effects of rIFN-· in our cases with PV.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Efficacy of Recombinant Interferon-Alpha in Polycythaemia vera

Öztürk¹,

Günay²,

Üskent³

1998

Acta Haematol

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The therapeutic efficacy of recombinant interferon-α (rIFN-α) has been evaluated in 7 patients with polycythaemia vera (PV), diagnosed according to the criteria of the Polycythemia Vera Study Group. Six complete responses and one partial response were achieved. Pruritus significantly improved in 80% (4/5) of the cases. Recombinant interferon-α had to be discontinued in 1 patient because of grade 3–4 nephrotoxicity according to WHO criteria. rIFN-α therapy significantly decreased the phlebotomy requirements and improved the mean corpuscular volume, erythrocyte and platelet counts, pruritus complaints and the degree of splenomegaly (p < 0.05). rIFN-α seems to be an effective treatment modality for the myeloproliferation of PV and pruritus complaints.

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Section: Discussionsupporting

confidence: 66%

Section: Methodsmentioning

confidence: 99%

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Therapeutic Efficacy of Recombinant Interferon-Alpha in Polycythaemia vera

Öztürk¹,

Günay²,

Üskent³

1998

Acta Haematol

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“…Untreated, the disease leads to thrombohemorrhagic complications and in most cases to progressive marrow myelofibrosis, anemia, and splenomegaly. 1 Long-term remission has been reported with recombinant interferon alpha (rIFN␣), [2][3][4][5][6][7] and, more recently, a number of patients have achieved complete or partial responses after treatment with imatinib mesylate. [8][9][10][11] rIFN␣ has been reported to induce cytogenetic remission in occasional patients and/or result in conversion of monoclonal to polyclonal hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha

Jones

Silver

Waghorn

et al. 2006

Blood

113

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Imatinib and recombinant interferon alpha (rIFN␣) can induce remission in polycythemia vera (PV) patients, but gauging the depth of responses has not been possible due to lack of a specific disease marker. We found that patients undergoing imatinib (n ‫؍‬ 14) or rIFN␣ (n ‫؍‬ 7) therapy remained strongly positive for V617F JAK2, although there was a significant reduction in the median percentage of mutant alleles that correlated with hematologic response (P ‫؍‬ .001). Furthermore, individuals who achieved complete hematologic remission had lower levels of V617F than those who did not (P ‫؍‬ .001). Of 9 imatinib-treated cases for whom pretreatment samples were available, 7 with no or partial hematologic responses showed a marginal increase (median, 1.2-fold; range, 1.0-1.5) in the percentage of V617F alleles on treatment, whereas the 2 patients who achieved complete hematologic remission showed a 2-to 3-fold reduction. Our data indicate that, although PV patients may benefit from imatinib or rIFN␣, molecular responses are relatively modest. (Blood. 2006;107: 3339-3341)

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“…17,18 IFN-␣ exerts antitumor activity in several types of neoplasm, including chronic myeloid leukemia, 19 Philadelphia chromosomenegative myeloproliferative disorder, hairy cell leukemia, and some solid tumors. [20][21][22][23] The molecular mechanisms that lead to tumor regression during IFN treatment are not fully elucidated. We hypothesized that CD95 and ligands of the death domain may belong to the group of IFN-stimulated genes and that IFN-␣ might induce apoptosis through an up-regulation of receptors and ligands of the death domain.…”

Section: Introductionmentioning

confidence: 99%

Autocrine cell suicide in a Burkitt lymphoma cell line (Daudi) induced by interferon α: involvement of tumor necrosis factor as ligand for the CD95 receptor

Gisslinger

Kurzrock

Gisslinger

et al. 2001

Blood

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IntroductionNumerous investigations have shown that growth inhibition and apoptosis are regulated by various oncogens and tumor suppressor genes. 1 The bcl-2 proto-oncogene product is one of the most efficient inhibitors of apoptosis in different cell types. 2 By analogy, 2 members of the tumor necrosis factor (TNF) receptor superfamily, TNF receptor type 1 (p55) and APO-1/Fas (CD95), can be considered proapoptotic tumor suppressor genes that lead to cell death 3-5 after activation by their ligands. 6,7 In a similar way, these ligands (TNF and APO-1/Fas-ligand [CD95L]) represent related type 2 membrane glycoproteins. Defects in CD95-mediated cell death may be responsible for some auto-immune diseases and may play a role in ontogeny. 8 An interaction of immunomodulating compounds with receptors and ligands of the death domain seem to be of high value in cancer treatment. Interferons (IFNs), the most prominent group of immunomodulating compounds, exert their pleiotropic biologic activities by the modulation of gene expression. Examples of well-characterized IFN-modulated genes and gene products are the major histocompatibility complex (MHC) antigens and the c-myc and retinoblastoma genes. 9-12 Enhancement of MHC antigens has been considered important in T-lymphocyte-mediated cytotoxicity. 13 IFN-␣ down-regulates the expression of c-myc and upregulates the retinoblastoma gene in a Burkitt lymphoma cell line (Daudi), and it has been assumed that these genes are closely involved in IFN-induced growth inhibition. 14-16 Recently, IFNs have been shown to enhance CD95 expression and to induce apoptosis in various cell systems. However, the activation of ligands of the death domain could not be observed in these experiments. 17,18 IFN-␣ exerts antitumor activity in several types of neoplasm, including chronic myeloid leukemia, 19 Philadelphia chromosomenegative myeloproliferative disorder, hairy cell leukemia, and some solid tumors. [20][21][22][23] The molecular mechanisms that lead to tumor regression during IFN treatment are not fully elucidated. We hypothesized that CD95 and ligands of the death domain may belong to the group of IFN-stimulated genes and that IFN-␣ might induce apoptosis through an up-regulation of receptors and ligands of the death domain. In the present study, we investigated whether the CD95 receptor/ligand system is involved in IFN-induced cell death and whether the CD95 receptor might be activated by cross-reactivity with TNF-␣. Materials and methods Cell cultures and IFNIFN-sensitive Daudi cells were grown between 1 and 5 days in RPMI 1640 medium (Gibco BRL/Life Technologies, Paisley, United Kingdom) supplemented with 10% fetal calf serum (FCS, Gibco BRL). In addition, cells For personal use only. on March 31, 2019. by guest www.bloodjournal.org From were incubated for up to 5 days in RPMI 1640 ϩ 10% FCS containing 200 U/mL recombinant (rec) human IFN-␣2a (Roferon-A; Hoffmann La Roche, Basel, Switzerland). IFN-resistant Daudi cells and the lymphoblastoid cell line Raji served as controls in the s...

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Efficacy of recombinant interferon‐alpha (rIFN‐α) in polycythaemia vera: a study of 17 patients and an analysis of published data

Cited by 43 publications

References 18 publications

Therapeutic Efficacy of Recombinant Interferon-Alpha in Polycythaemia vera

Therapeutic Efficacy of Recombinant Interferon-Alpha in Polycythaemia vera

Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha

Autocrine cell suicide in a Burkitt lymphoma cell line (Daudi) induced by interferon α: involvement of tumor necrosis factor as ligand for the CD95 receptor

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