Intensification of Chemotherapeutic Regimens and Hematopoietic Stem Cell Transplantation Are Responsible for Improved Overall Survival in Adult Acute Lymphoblastic Leukemia in a Single Center Over the Last Forty Years
Authors: Carrillo Estrella , Rodriguez Nancy , Dominguez Juan Francisco , Gonzalez Jose , Falantes Jose Francisco , Montero Isabel , Martino M. Luz , Márquez-Malaver Francisco , Parody Ricardo , Garcia-Guerrero Estefania , Perez-Simón Jose Antonio , Espigado Ildefonso 
Published: October 2019

Abstract
Abstract 4227

Background
Acute lymphoblastic leukemia (ALL) of adults is an infrequent and heterogeneous disease according to presentation pattern, prognosis and treatment. It is widely assumed that age above 30 years, leukocytosis >25 ×109/L, central nervous system involvement and specific cytogenetic disorders such as t(9;22) or MLL rearrangement entail bad prognosis. There are controversial studies on the impact of intensification chemotherapy and hematopoietic stem cell transplantation (HSCT) on survival of these high-risk groups.

Aims
To identify biological, clinical and prognostic characteristics in adult ALL patients diagnosed and followed in a single center throughout 40 years as long as the impact on clinical outcome of different consecutive therapeutic approaches, including HSCT, in different periods.

Patients and methods
Throughout 1970 to 2011, 230 patients were prospectively registered and retrospectively analyzed. Most patients accomplishing pre-determined criteria received treatment according to PETHEMA or locally developed therapeutic protocols (including HSCT in relapse high-risk patients, since 1978). Critical variables at diagnosis such as age, gender, phenotype (from 1978), cytogenetic (from 1999), white blood cells count (WBC) and central nervous system involvement, were analyzed.
Response to induction chemotherapy, relapse rate (RR) and 5 year overall survival (OS) were analyzed in the whole cohort and separately by decade when treatment protocols were different. The clinical impact of HSCT was analyzed on a subgroup of patients homogeneously treated since 1994. Statistical analysis was performed by mean of Chi-square and Kaplan Meier tests, as appropriate.

Outcome
Table 1 summarizes the presentation pattern and its prognostic value. At diagnosis features such male gender, age above 30 years, central nervous system involvement, leukocytosis >10×109/L, MLL rearrangement, t(9:22) and complex karyotype entailed a worse prognosis. For the whole cohort the 5 years OS was 30%. CR was achieved in 73% and the RR was 38%. 5 years OS has improved by decades: 11% in the 70s, 24% in the 80s, 30% in the 90s, and 41% in XXI century (p<0,01). Patients selected for intensive chemotherapeutic protocols achieved a similar CR rate in each decade (nearly 80%) while the RR decreased through the years (70s: 68%, 80s: 44%, 90: 42%, 00–11: 25%; p<0,01). Patients treated with chemotherapy plus HSCT achieved in 5 years (from 1994) an OS of 69% in comparison with the 30% obtained in those patients who only received chemotherapy (p<0,01).

Conclusion
Male gender, age above 30, WBC >10×10e9/L, t(9;22), MLL-rearrangement, complex karyotype and CNS involvement conferred poor prognosis in adult ALL. Intensification of chemotherapeutic regimens produced a progressive decrease in relapse rate, leading to an improvement in overall survival over the years. HSCT seems to partially overcome the poor prognosis related to high risk factors.

Disclosures:
Perez-Simón: Janssen-Cilag: Patents & Royalties.