Randomized, parallel-group comparison of interferon alfa-2b plus hydroxyurea versus hydroxyurea alone in patients with chronic myelogenous leukaemia in chronic phase

Chong Won Park , Chi Hwa Han , Choon Choo Kim , Dong Jip Kim
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引用次数: 1

Abstract

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.

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
一项研究比较了重组干扰素α -2b (IFN α -2b)联合羟基脲(HU)与单独羟基脲(HU)对慢性粒细胞白血病(CML)患者血液学缓解(HR)的影响。21例患者随机接受IFN α -2b + HU治疗(n = 12;7男5女;平均年龄40岁,范围29-57岁)或单纯HU (n = 9;三男六女;平均年龄35岁,范围24-50岁)。所有患者最初都接受单独的HU细胞减少治疗,剂量根据白细胞(WBC)计数。当白细胞计数降至5 - 10 × 103/μl时,患者随机接受每天200万单位皮下注射IFN α -2b +调整日剂量HU (>150 × 103/μl, 4g;50−150 × 103/μl, 3g;30−50 × 103/μl, 2g;10−30 × 103/μl, 1g;和5−10 × 103/μl (0g),或单独使用HU。因此,患者在WBC计数上升到5−10 × 103/μl以上时才接受HU治疗。根据Ph1染色体的百分比进行亚分类:A1, Ph1染色体存在于所有可分析的中期;35-59%存在A2、Ph1染色体;A3, 5 - 34%;A4, Ph1染色体在所有可分析的中期缺失。B[PHR]: B1,外周血白细胞计数减少至少50%至<20 × 103/μl;B2,外周血白细胞计数正常,但未成熟形态持续存在或临床可触及脾肿大。失败:未能达到上述PHR或CHR的患者)。利用两组引物对序列编码bcr-abl mRNA (A引物:5 ' -GGAGCTGCAGATGCTGACCAAC-3 '编码bcr外显子II;B引物:5 ' -TCAGACCCTGAGGCTCAAAGTC-3 '编码abl外显子II;A '引物:5 ' -CCTGATCTCCTCTGA ctagag -3 '编码bcr外显子I;B '引物:5 ' -TCCAGCGAGAAGGTTTTCCTTG-3 '编码abl外显子I),我们进行了cDNA-PCR分析,发现在两例IFN诱导的CHR患者的外周单核细胞中持续表达bcr-abl mRNA。我们建议IFN治疗至少应该持续到分子缓解。
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