Estey E H, Giles F J, Kantarjian H, O'Brien S, Cortes J, Freireich E J, Lopez-Berestein G, Keating M
Department of Leukemia Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Blood. 1999 Oct 1;94(7):2230-5.
All-trans retinoic acid administered orally (oral ATRA) may not regularly lead to either molecular complete remissions (CRs) or prolonged hematologic CRs (HCR) unless combined with chemotherapy. Because serum tretinoin concentrations are higher, and maintained longer, after use of liposomal-encapsulated ATRA (lipoATRA) rather than oral ATRA, we investigated lipoATRA monotherapy in newly diagnosed acute promyelocytic leukemia (APL). Patients received lipoATRA 90 mg/m(2) every other day for remission induction. The same dose was given 3 times a week until 9 months had elapsed from HCR date. Treatment then stopped. Chemotherapy (idarubicin 12 mg/m(2) daily days 1-2 for 2 courses) was to be added only if 2 polymerase chain reaction (PCR) tests, performed 2 weeks apart, were positive at 3, 6, or 9 months from HCR date. The sensitivity level of the PCR was 10(-4). We treated 18 patients (median age, 54 years; median white blood cell [WBC] count 4,500/microL). The HCR rate was 12/18 (67%, 95% confidence interval [CI], 41% to 87%). This rate was similar to that we observed in a previous study using oral ATRA + idarubicin. Nine of 10 patients studied at HCR date were PCR-positive. Subsequently, however, overall (+/- idarubicin) rates of PCR positivity were 0/12 at 3 months, 1/10 at 6 months, 1/7 at 9 and 12 months, and 0/4 at 15 to 17 months. Idarubicin has been added in 3 patients, with this addition occurring at 6 months in 2 patients and at 9 months in 1 patient. Among patients who had not received idarubicin when the PCR was evaluated, 0 of 12 were PCR-positive at 3 months, 1 of 10 was positive at 6 months, 1 of 6 was positive at 9 months, 0 of 4 were positive at 12 months, and 0 of 3 were positive at 15 to 17 months. Morphologic APL has recurred in 1 patient, with a median follow-up time of 13 months in the 11 patients remaining in first CR. The median follow-up time is 91/2 months (range, 3 to 17) in the 9 patients who have received only lipoATRA and who remain PCR-negative and in first CR. Our data suggest that lipoATRA is an effective means of producing molecular CR in newly diagnosed APL.
口服全反式维甲酸（口服ATRA）通常不会常规导致分子完全缓解（CRs）或延长血液学CR（HCR），除非与化疗联合使用。由于使用脂质体包裹的ATRA（lipoATRA）后血清维甲酸浓度更高且维持时间更长，我们研究了lipoATRA单药治疗新诊断的急性早幼粒细胞白血病（APL）。患者接受lipoATRA 90 mg/m²，隔日一次进行缓解诱导。从HCR日期起每周3次给予相同剂量，直至9个月。然后停止治疗。仅在距HCR日期3、6或9个月时，间隔2周进行的2次聚合酶链反应（PCR）检测呈阳性时，才添加化疗（伊达比星12 mg/m²，第1 - 2天每日给药，共2个疗程）。PCR的灵敏度水平为10⁻⁴。我们治疗了18例患者（中位年龄54岁；中位白细胞[WBC]计数4500/μL）。HCR率为12/18（67%，95%置信区间[CI]，41%至87%）。该率与我们之前使用口服ATRA +伊达比星的研究中观察到的相似。在HCR日期研究的10例患者中有9例PCR阳性。然而，随后，总体（±伊达比星）PCR阳性率在3个月时为0/12，6个月时为1/10，9个月和12个月时为1/7，15至17个月时为0/4。3例患者添加了伊达比星，2例患者在6个月时添加，1例患者在9个月时添加。在评估PCR时未接受伊达比星的患者中，3个月时12例中有0例PCR阳性，6个月时10例中有1例阳性，9个月时6例中有1例阳性，12个月时4例中有0例阳性，15至17个月时3例中有0例阳性。1例患者出现形态学APL复发，11例处于首次CR的患者中位随访时间为13个月。在仅接受lipoATRA且仍为PCR阴性并处于首次CR的9例患者中，中位随访时间为9.5个月（范围3至17个月）。我们的数据表明，lipoATRA是在新诊断的APL中产生分子CR的有效方法。
