Lack of Prognostic Significance of Monosomal Karyotype and Absolute Lymphocyte Count At Diagnosis in Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia

Monosomal Karyotype (MK) is defined as the presence of two or more autosomal monosomies or one autosomal monosomy and one structural abnormality. MK has been found to be an independent poor prognostic factor in myeloid diseases (Patnaik et al, Leukemia 2011, Haferlach et al, Blood 2012) even in the setting of allogeneic stem cell transplantation (Fang et al, Blood 2011). The prognostic relevance of MK in Acute Lymphoblastic Leukemia (ALL) is unknown. Absolute lymphocyte count (ALC) at diagnosis, on the other hand, has been shown to be prognostic in a variety of lymphoproliferative disorders (Porrata et al, Leukemia 2010). However, the prognosis of ALC at diagnosis in ALL is undetermined

This is a retrospective analysis of the Mayo Clinic leukemia database (1998–2010). The study was approved by the Institutional Review Board. Outcomes analyzed included overall survival (OS), leukemia free survival (LFS) and relapse rate. Clinical characteristics, cytogenetics, therapy and outcomes of patients with Philadelphia negative ALL (Ph-negative ALL) were analyzed. Cytogenetics were classified as follows: standard risk [hyperdiploidy], intermediate risk [Normal, del(11q)-not MLL, del(6q), del(17p), del(9p), del(12p), del(13q), t(14q32), t(10;14), low hyperdiploidy, others], high risk [-7, del(7p), +8, MLL translocations, t(1;19), t(17;19), t(5;14)], and very high [t(4;11), t(8;14), complex (≥5 abnormalities), hypodiploidy, triploidy] (Pullarkat et, Blood 2008). Multivariate analysis was performed using Cox Regression Model.

Between 1998 and 2010, a total of 175 consecutive patients with ALL were identified. Of these, 112 (64%) had Ph-negative ALL. The median age was 39.5 (16–88) years and 74 were male (66%). The majority of cases were B-ALL (78 patients, 69%). At presentation, the median hemoglobin was 10 (4.1–18.5) g/dL, platelet count was 61 (3–523) ×10(9)/L, WBC was 7.2 (0.8–377) ×10(9)/L and ALC was 1.9 (0–69.0) ×10(9)/L. The ALC was > 1000 in 75 (71%) patients. Cytogenetics risk categories were as follows: standard risk in 5 (4.4%), intermediate risk in 70 (62.5%), high risk in 8 (7.1%) and very high risk in 29 (25.9%) patients. Twenty-two patients (20.9%) presented with extranodal disease (CNS disease in 13 patients, 11.6%). Six patients (5.4%) had prior exposure to chemotherapy. Treatment involved allogeneic stem cell transplantation (SCT) in 34 (30.4%) patients. The median OS for the whole cohort was 24 (0–206) months and LFS was 18 (0–193) months. Forty four patients (39.3%) relapsed after achieving initial remission with a median time to relapse of 15 (2–73) months

In a univariate analysis, low platelet count at diagnosis, poor ECOG performance status (PS), and high or very high risk cytogenetics risk categories were associated with inferior OS. ALC at diagnosis did not impact OS or LFS. On a multivariate analysis, high/very high risk cytogenetics, low platelet counts and poor ECOG PS were independent predictors of inferior outcomes.

Nineteen patients (16.9%) had a MK. Of these, 16 (84.2%) fell in the very high risk cytogenetics category regardless of MK status. Three patients (1.6%) presented with extramedullary disease and six (3.2%) underwent SCT. The median OS of these 19 patients was 15 (1–73) months. While MK was associated with inferior LFS and a trend towards worse OS, this was not significant on a multivariate model that included cytogenetic risk categories, thrombocytopenia and the ECOG PS.

Our study demonstrates that cytogenetics risk stratification, thrombocytopenia and ECOG performance status are independent prognostic factors in ALL. MK and ALC at diagnosis had no prognostic significance.

No relevant conflicts of interest to declare.