Chong Won Park , Chi Hwa Han , Choon Choo Kim , Dong Jip Kim
{"title":"干扰素α -2b联合羟基脲与单独应用羟基脲治疗慢性粒细胞白血病慢性期患者的随机、平行组比较","authors":"Chong Won Park , Chi Hwa Han , Choon Choo Kim , Dong Jip Kim","doi":"10.1016/0277-5379(91)90563-S","DOIUrl":null,"url":null,"abstract":"<div><p>A STUDY was undertaken to compare the effect of recombinant interferon alfa-2b (IFN alfa-2b) plus hydroxyurea (HU) with that of HU alone on haematological remission (HR) in patients with chronic phase chronic myelogenous leukaemia (CML). Twenty-one patients were randomized to receive either IFN alfa-2b plus HU (<em>n</em> = 12; seven male and five female; mean age 40 years, range 29–57 years) or HU alone (<em>n</em> = 9; three male and six female; mean age 35 years, range 24–50 years). All patients initially received cytoreductive therapy with HU alone, at a dose according to the white blood cell (WBC) count. When the WBC count decreased to 5−10 × 10<sup>3</sup>/μl, patients were randomized to receive either IFN alfa-2b 2 million units per day by subcutaneous (s.c.) injection plus the adjusted daily dose of HU (> 150 × 10<sup>3</sup>/μl, 4g; 50−150 × 10<sup>3</sup>/μl, 3g; 30−50 × 10<sup>3</sup>/μl, 2g; 10−30 × 10<sup>3</sup>/μl, 1g; and 5−10 × 10<sup>3</sup>/μl, 0g), or HU alone. Thus, patients received no HU until their WBC count rose above 5−10 × 10<sup>3</sup>/μl. Eleven of 12 patients on IFN plus HU achieved a haematological response, including nine with complete haematological remission (CHR) (A1: <em>n</em> = 0, A2: <em>n</em> = 4, A3: <em>n</em> = 3, A4: <em>n</em> = 2) and two with partial haematological remission (PHR) (B1: <em>n</em> = 0, B2: <em>n</em> = 2), while none of the nine patients on HU alone achieved a remission with the above-mentioned doses of HU according to our criteria (A[CHR]: WBC count maintained below 9 × 10<sup>3</sup>/μl without blast and no symptoms or signs associated with CML; subclassified according to the percentage of Ph<sup>1</sup> chromosome: A1, Ph<sup>1</sup> chromosome present in all analyzable metaphases; A2, Ph<sup>1</sup> chromosome present in 35–59%; A3, 5–34%; A4, Ph<sup>1</sup> chromosome absent from all analyzable metaphases. B[PHR]: B1, reduction of peripheral WBC count by at least 50% to < 20 × 10<sup>3</sup>/μl; B2, normalization of peripheral WBC count but persistence of immature form or clinically palpable splenomegaly. Failure: patients who failed to achieve a PHR or CHR as defined above). Using two sets of primer pair sequences encoding bcr-abl mRNA (A primer: 5′-GGAGCTGCAGATGCTGACCAAC-3′ encoding bcr exon II; B primer: 5′-TCAGACCCTGAGGCTCAAAGTC-3′ encoding abl exon II; A′ primer: 5′-CCTGATCTCCTCTGA CTATGAG-3′ encoding bcr exon I; B′ primer: 5′-TCCAGCGAGAAGGTTTTCCTTG-3′ encoding abl exon I), we performed the cDNA-PCR analysis, which revealed persistent bcr-abl mRNA expression in the peripheral mononuclear cells from two patients who achieved CHR induced by IFN. We suggest that IFN therapy should be continued at least until molecular remission is achieved.</p></div>","PeriodicalId":11925,"journal":{"name":"European Journal of Cancer and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0277-5379(91)90563-S","citationCount":"1","resultStr":"{\"title\":\"Randomized, parallel-group comparison of interferon alfa-2b plus hydroxyurea versus hydroxyurea alone in patients with chronic myelogenous leukaemia in chronic phase\",\"authors\":\"Chong Won Park , Chi Hwa Han , Choon Choo Kim , Dong Jip Kim\",\"doi\":\"10.1016/0277-5379(91)90563-S\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>A STUDY was undertaken to compare the effect of recombinant interferon alfa-2b (IFN alfa-2b) plus hydroxyurea (HU) with that of HU alone on haematological remission (HR) in patients with chronic phase chronic myelogenous leukaemia (CML). Twenty-one patients were randomized to receive either IFN alfa-2b plus HU (<em>n</em> = 12; seven male and five female; mean age 40 years, range 29–57 years) or HU alone (<em>n</em> = 9; three male and six female; mean age 35 years, range 24–50 years). All patients initially received cytoreductive therapy with HU alone, at a dose according to the white blood cell (WBC) count. When the WBC count decreased to 5−10 × 10<sup>3</sup>/μl, patients were randomized to receive either IFN alfa-2b 2 million units per day by subcutaneous (s.c.) injection plus the adjusted daily dose of HU (> 150 × 10<sup>3</sup>/μl, 4g; 50−150 × 10<sup>3</sup>/μl, 3g; 30−50 × 10<sup>3</sup>/μl, 2g; 10−30 × 10<sup>3</sup>/μl, 1g; and 5−10 × 10<sup>3</sup>/μl, 0g), or HU alone. Thus, patients received no HU until their WBC count rose above 5−10 × 10<sup>3</sup>/μl. Eleven of 12 patients on IFN plus HU achieved a haematological response, including nine with complete haematological remission (CHR) (A1: <em>n</em> = 0, A2: <em>n</em> = 4, A3: <em>n</em> = 3, A4: <em>n</em> = 2) and two with partial haematological remission (PHR) (B1: <em>n</em> = 0, B2: <em>n</em> = 2), while none of the nine patients on HU alone achieved a remission with the above-mentioned doses of HU according to our criteria (A[CHR]: WBC count maintained below 9 × 10<sup>3</sup>/μl without blast and no symptoms or signs associated with CML; subclassified according to the percentage of Ph<sup>1</sup> chromosome: A1, Ph<sup>1</sup> chromosome present in all analyzable metaphases; A2, Ph<sup>1</sup> chromosome present in 35–59%; A3, 5–34%; A4, Ph<sup>1</sup> chromosome absent from all analyzable metaphases. B[PHR]: B1, reduction of peripheral WBC count by at least 50% to < 20 × 10<sup>3</sup>/μl; B2, normalization of peripheral WBC count but persistence of immature form or clinically palpable splenomegaly. Failure: patients who failed to achieve a PHR or CHR as defined above). Using two sets of primer pair sequences encoding bcr-abl mRNA (A primer: 5′-GGAGCTGCAGATGCTGACCAAC-3′ encoding bcr exon II; B primer: 5′-TCAGACCCTGAGGCTCAAAGTC-3′ encoding abl exon II; A′ primer: 5′-CCTGATCTCCTCTGA CTATGAG-3′ encoding bcr exon I; B′ primer: 5′-TCCAGCGAGAAGGTTTTCCTTG-3′ encoding abl exon I), we performed the cDNA-PCR analysis, which revealed persistent bcr-abl mRNA expression in the peripheral mononuclear cells from two patients who achieved CHR induced by IFN. We suggest that IFN therapy should be continued at least until molecular remission is achieved.</p></div>\",\"PeriodicalId\":11925,\"journal\":{\"name\":\"European Journal of Cancer and Clinical Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1991-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/0277-5379(91)90563-S\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Cancer and Clinical Oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/027753799190563S\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer and Clinical Oncology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/027753799190563S","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Randomized, parallel-group comparison of interferon alfa-2b plus hydroxyurea versus hydroxyurea alone in patients with chronic myelogenous leukaemia in chronic phase
A STUDY was undertaken to compare the effect of recombinant interferon alfa-2b (IFN alfa-2b) plus hydroxyurea (HU) with that of HU alone on haematological remission (HR) in patients with chronic phase chronic myelogenous leukaemia (CML). Twenty-one patients were randomized to receive either IFN alfa-2b plus HU (n = 12; seven male and five female; mean age 40 years, range 29–57 years) or HU alone (n = 9; three male and six female; mean age 35 years, range 24–50 years). All patients initially received cytoreductive therapy with HU alone, at a dose according to the white blood cell (WBC) count. When the WBC count decreased to 5−10 × 103/μl, patients were randomized to receive either IFN alfa-2b 2 million units per day by subcutaneous (s.c.) injection plus the adjusted daily dose of HU (> 150 × 103/μl, 4g; 50−150 × 103/μl, 3g; 30−50 × 103/μl, 2g; 10−30 × 103/μl, 1g; and 5−10 × 103/μl, 0g), or HU alone. Thus, patients received no HU until their WBC count rose above 5−10 × 103/μl. Eleven of 12 patients on IFN plus HU achieved a haematological response, including nine with complete haematological remission (CHR) (A1: n = 0, A2: n = 4, A3: n = 3, A4: n = 2) and two with partial haematological remission (PHR) (B1: n = 0, B2: n = 2), while none of the nine patients on HU alone achieved a remission with the above-mentioned doses of HU according to our criteria (A[CHR]: WBC count maintained below 9 × 103/μl without blast and no symptoms or signs associated with CML; subclassified according to the percentage of Ph1 chromosome: A1, Ph1 chromosome present in all analyzable metaphases; A2, Ph1 chromosome present in 35–59%; A3, 5–34%; A4, Ph1 chromosome absent from all analyzable metaphases. B[PHR]: B1, reduction of peripheral WBC count by at least 50% to < 20 × 103/μl; B2, normalization of peripheral WBC count but persistence of immature form or clinically palpable splenomegaly. Failure: patients who failed to achieve a PHR or CHR as defined above). Using two sets of primer pair sequences encoding bcr-abl mRNA (A primer: 5′-GGAGCTGCAGATGCTGACCAAC-3′ encoding bcr exon II; B primer: 5′-TCAGACCCTGAGGCTCAAAGTC-3′ encoding abl exon II; A′ primer: 5′-CCTGATCTCCTCTGA CTATGAG-3′ encoding bcr exon I; B′ primer: 5′-TCCAGCGAGAAGGTTTTCCTTG-3′ encoding abl exon I), we performed the cDNA-PCR analysis, which revealed persistent bcr-abl mRNA expression in the peripheral mononuclear cells from two patients who achieved CHR induced by IFN. We suggest that IFN therapy should be continued at least until molecular remission is achieved.