Ribera Josep-Maria, Ortega Juan-José, Oriol Albert, Granada Isabel, Hernández-Rivas Jesús-Maria, Parody Ricardo, Bethencourt Concepción, Rivas Concepción, Bastida Pilar, del Potro Eloy, González-Valentín Maria-Elvira, Moreno María-José, Besalduch Joan, Fernández-Calvo Javier, Tormo Mar, Arias Jesús, Molinés Antonio, Sanz Miguel Angel, Maldonado Juan, Millá Fuensanta, Feliu Evarist, San Miguel Jesús-Fernando
Hematology Department and Hematopoietic Progenitor Transplant Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Haematologica. 2002 Feb;87(2):154-66.
Cytogenetic analysis is one of the most reliable prognostic factors in acute lymphoblastic leukemia. The objective of this study was to analyze the prognostic value of cytogenetic analysis in children and adults with high-risk acute lymphoblastic leukemia (HR-ALL) included in a prospective multicenter trial.
One hundred and thirty patients (44 children and 86 adults) with HR-ALL included in the PETHEMA ALL-93 trial had an adequate cytogenetic study after review. Cytogenetic subgroups were established according to the cancer and acute leukemia group B criteria (unfavorable: 11q23, t(9;22), -7 and +8; normal; miscellaneous: the remaining chromosome abnormalities) and their main clinicobiological features were compared. Univariable and multivariable analyses for complete remission (CR) attainment, event-free survival (EFS) and overall survival (OS) were performed.
The mean SD age was 26 14 years. Two were infants (<1 year), 42 were children and 86 adults (19-50 years). The cytogenetic study was normal in 44 (34%) cases. The most frequent chromosomal rearrangement was t(9;22)(q34;q11) (34 cases, 26%, 30 adults), followed by 11q23 (12 cases, 9% -8 children-, including t(4;11)(q21;q23) in 8, 7 children). Patients with t(9;22) were older than the remaining cases, whereas those with 11q23 rearrangements were younger and had higher WBC counts. Multivariable analyses showed two associated factors in adults with a lower frequency of CR and a shorter EFS and OS: t(9;22) and slow response to therapy (assessed by a percentage of blast cells higher than 10% in bone marrow study on day 14). For children with very high-risk ALL, only slow response to therapy (assessed by the presence of blast cells in peripheral blood on day 8) was associated with a negative impact on CR, EFS and OS.
In adult patients with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 protocol, cytogenetic analysis at diagnosis is a useful independent prognostic marker. The poorest prognosis for patients with t(9;22) justifies the development of specific treatments for these patients. In this small subgroup of children with very high-risk ALL no cytogenetic characteristics was found to influence the results of therapy, slow response to therapy being the only prognostic factor.
细胞遗传学分析是急性淋巴细胞白血病最可靠的预后因素之一。本研究的目的是分析细胞遗传学分析在一项前瞻性多中心试验中纳入的高危急性淋巴细胞白血病（HR-ALL）儿童和成人患者中的预后价值。
PETHEMA ALL-93试验纳入的130例HR-ALL患者（44例儿童和86例成人）经复查后进行了充分的细胞遗传学研究。根据癌症和急性白血病B组标准建立细胞遗传学亚组（不良组：11q23、t(9;22)、-7和+8；正常组；其他组：其余染色体异常），并比较其主要临床生物学特征。对完全缓解（CR）率、无事件生存期（EFS）和总生存期（OS）进行单变量和多变量分析。
平均标准差年龄为26±14岁。2例为婴儿（<1岁），42例为儿童，86例为成人（19-50岁）。44例（34%）患者的细胞遗传学研究结果正常。最常见的染色体重排是t(9;22)(q34;q11)（34例，26%，30例成人），其次是11q23（12例，9%，8例儿童，其中8例（7例儿童）为t(4;11)(q21;q23)）。t(9;22)患者比其余患者年龄大，而11q23重排患者年龄较小且白细胞计数较高。多变量分析显示，成人中CR率较低、EFS和OS较短的两个相关因素为：t(9;22)和对治疗反应缓慢（通过第14天骨髓研究中原始细胞百分比高于10%评估）。对于极高危ALL儿童，仅对治疗反应缓慢（通过第8天外周血中原始细胞的存在评估）与对CR、EFS和OS有负面影响相关。
在PETHEMA ALL-93方案纳入的高危急性淋巴细胞白血病成人患者中，诊断时的细胞遗传学分析是一个有用的独立预后标志物。t(9;22)患者预后最差，这为针对这些患者开发特异性治疗方法提供了依据。在这个极小的极高危ALL儿童亚组中，未发现细胞遗传学特征影响治疗结果，对治疗反应缓慢是唯一的预后因素。
