Ludwig W D, Rieder H, Bartram C R, Heinze B, Schwartz S, Gassmann W, Löffler H, Hossfeld D, Heil G, Handt S, Heyll A, Diedrich H, Fischer K, Weiss A, Völkers B, Aydemir U, Fonatsch C, Gökbuget N, Thiel E, Hoelzer D
Medizinische Fakultät Charité, Humboldt-Universität, Robert-Rössle-Klinik, Berlin, Germany; the Klinikum der Philipps-Universität, Marburg, Germany; Universitätsklinikum, Heidelberg, Germany.
Blood. 1998 Sep 15;92(6):1898-909.
In contrast to childhood acute lymphoblastic leukemia (ALL), the cell-biological features, clinical characteristics, and treatment outcome of CD10(-) pro-B ALL have not yet been determined in larger series of adult patients. Therefore, we studied 57 adult patients with newly diagnosed pro-B ALL (median age, 30 years) enrolled in two consecutive German multicenter ALL studies (03/87 and 04/89). Extensive immunophenotypic characterization of leukemic blasts could be performed on all patients, whereas adequate cytogenetic data were available in 33 cases and molecular studies in 18 cases, using reverse transcription-polymerase chain reaction to detect MLL-AF-4 transcripts. Twenty-two patients demonstrated a t(4;11)(q21;q23) and/or MLL-AF-4 rearrangements, and 6 patients had other structural abnormalities, including a t(9;22)(q34;q11) (N = 2). Nine patients had a normal karyotype. Patients with 11q23 abnormalities tended to be younger (median age, 29 years) and were characterized by male predominance (64%), hyperleukocytosis (median leukocyte count, 168 x 10(9)/L), and a frequent coexpression of CD65s (64%) as compared with patients with other cytogenetic abnormalities or a normal karyotype. Twelve of 16 (75%) pro-B ALL patients in study 03/87 and 30 of 41 (73%) in study 04/89 achieved a complete remission (CR). Sixteen of 30 patients in study 04/89 remain in continuous CR (CCR) in contrast to only 2 of 12 patients in study 03/87. Interestingly, all 7 patients treated with high-dose cytarabine and mitoxantrone as consolidation in study 04/89 remain alive and leukemia-free. One patient in study 03/87 and 8 in study 04/89 underwent autologous (N = 2) or allogeneic (N = 7) bone marrow transplantation (BMT). The median remission duration was 420 days for patients in study 03/87 and has not yet been reached in study 04/89. The median survival time of all pro-B ALL patients was 571 days in study 03/87 and 747 days in study 04/89. Among the 22 patients with a t(4;11) and/or MLL-AF-4 rearrangements, 17 achieved a CR and 8 are still in CCR, of whom 4 underwent an allogeneic BMT. Remission duration and overall survival did not differ significantly between pro-B ALL patients with 11q23 abnormalities and those with a normal karyotype or other structural abnormalities. These data indicate that intensification of postremission treatment may improve the prognosis of adult pro-B ALL, including patients with a t(4;11).
与儿童急性淋巴细胞白血病（ALL）不同，CD10(-)前B-ALL的细胞生物学特征、临床特点及治疗结果在大量成年患者中尚未明确。因此，我们研究了连续两项德国多中心ALL研究（03/87和04/89）中纳入的57例新诊断的前B-ALL成年患者（中位年龄30岁）。所有患者均对白血病原始细胞进行了广泛的免疫表型特征分析，33例患者有足够的细胞遗传学数据，18例患者进行了分子研究，采用逆转录-聚合酶链反应检测MLL-AF-4转录本。22例患者表现为t(4;11)(q21;q23)和/或MLL-AF-4重排，6例患者有其他结构异常，包括t(9;22)(q34;q11)（2例）。9例患者核型正常。与其他细胞遗传学异常或核型正常的患者相比，11q23异常的患者往往更年轻（中位年龄29岁），以男性为主（64%），白细胞增多（中位白细胞计数168×10⁹/L），且CD65s共表达频繁（64%）。在03/87研究中，16例前B-ALL患者中有12例（75%）达到完全缓解（CR），在04/89研究中，41例中有30例（73%）达到CR。04/89研究中30例患者中有16例仍处于持续完全缓解（CCR），而03/87研究中12例患者中只有2例。有趣的是，在04/89研究中接受大剂量阿糖胞苷和米托蒽醌巩固治疗的所有7例患者均存活且无白血病。03/87研究中有1例患者和04/89研究中有8例患者接受了自体（2例）或异基因（7例）骨髓移植（BMT）。03/87研究中患者的中位缓解期为420天，04/89研究中尚未达到。所有前B-ALL患者的中位生存时间在03/87研究中为571天，在04/89研究中为747天。在22例有t(4;11)和/或MLL-AF-4重排的患者中，17例达到CR，8例仍处于CCR，其中4例接受了异基因BMT。11q23异常的前B-ALL患者与核型正常或有其他结构异常的患者之间，缓解期和总生存期无显著差异。这些数据表明，缓解后治疗的强化可能改善成年前B-ALL患者的预后，包括有t(4;11)的患者。
