Abstract
Simple SummaryAnaplastic large cell lymphoma (ALCL) is a systemic peripheral T-cell neoplasm characterized by strong and uniform CD30 expression and, usually, the aberrant loss of one or more T-cell antigens. ALCL is further classified into anaplastic lymphoma kinase (ALK)-positive and ALK-negative types. ALCL rarely involves the peripheral blood. The reported leukemic phase ALCL cases are almost all pediatric patients with ALK-positive ALCL, which are frequently associated with the small cell morphology, t(2;5)(p23;q35), and a poorer prognosis. Leukemic phase ALK-negative ALCL is extremely rare, with approximately ten cases reported in the literature to date, mostly as single case reports. Here we report on nine patients with leukemic ALK-negative ALCL—the largest case series to date—and we compare these cases with 39 non-leukemic cases of ALK-negative ALCL. We show that the patients with leukemic ALK-negative ALCL have a greater frequency of absolute lymphocytosis, thrombocytopenia, bone marrow involvement, CD7 positivity, complex karyotype, TP53 deletion, and a dismal outcome. These data suggest that leukemic phase ALK-negative ALCL is associated with a number of poor prognostic factors and affected patients may need more aggressive treatment.Patients with anaplastic large cell lymphoma (ALCL) rarely develop a leukemic phase of the disease. The reported leukemic ALCL cases are almost all ALK-positive, which are frequently associated with small cell morphology, t(2;5)(p23;q35), and a poorer prognosis. Rare leukemic ALK-negative ALCL cases have been reported. In the present study, we investigated the clinical and pathologic features and outcomes of nine patients with leukemic ALK-negative ALCL and compared these features with 39 patients without leukemic disease. Compared with the non-leukemic ALK-negative ALCL group, patients with leukemic disease more often had absolute lymphocytosis (50% vs. 0%, p = 0.008), thrombocytopenia (60% vs. 11%, p = 0.03), bone marrow involvement (50% vs. 14%, p = 0.04), and CD7 positivity (71% vs. 19%, p = 0.02). Four of five (80%) patients with leukemic ALK-negative ALCL had a complex karyotype, which was significantly higher than that of the patients in the non-leukemic group. A fluorescence in situ hybridization for TP53 was performed on six leukemic ALK-negative ALCL cases and all (100%) had TP53 deletion. There were no significant differences in the other clinicopathologic features, treatment, and complete remission rates between patients in the leukemic versus non-leukemic group (all p > 0.05). The median follow-up of this cohort was 18 months with a range of 0.3–140 months. Eight of nine (90%) patients with leukemic ALK-negative ALCL died, and their overall survival was significantly shorter than that of the patients with non-leukemic disease (median 15.5 vs. 60 months, p = 0.001). In conclusion, we show that the leukemic phase of ALK-negative ALCL is associated with high-risk biologic features and, in particular, a complex karyotype and TP53 deletion. Compared with the non-leukemic ALK-negative ALCL patients, the patients with a leukemic phase of disease have poorer survival and may require more aggressive treatment.
Highlights
Anaplastic large cell lymphoma (ALCL) is a systemic peripheral T-cell neoplasm with strong and uniform CD30 expression, which is usually associated with aberrant loss of one or more T-cell antigens
The clinical features of nine patients with leukemic anaplastic lymphoma kinase (ALK)-negative ALCL at time of initial diagnosis are summarized in Tables 1 and 2
The serum lactate dehydrogenase (LDH) levels were elevated in all three patients tested
Summary
Anaplastic large cell lymphoma (ALCL) is a systemic peripheral T-cell neoplasm with strong and uniform CD30 expression, which is usually associated with aberrant loss of one or more T-cell antigens. The lymphoma cells usually grow in a cohesive pattern, and when nodal architecture is preserved, they can infiltrate sinuses or selectively involve paracortical areas. ALCL is further classified into anaplastic lymphoma kinase (ALK)-positive (+) and ALK-negative types [1]. ALK+ ALCL is characterized by translocations involving ALK at 2p23, most commonly t(2;5)(p23;q35)/NPM1::ALK, which leads to strong and uniform ALK expression. In the current World Health Organization (WHO) classification, ALK+ ALCL cases are further divided into five variants based on their morphologic features: common, small cell, lymphohistiocytic, Hodgkin-like, and a composite pattern. Patients with ALK-negative ALCL are usually older than those with ALK+ ALCL and have less extra-nodal involvement and a poorer outcome. The long-term overall survival rates of patients with ALK+ and ALK-negative ALCL are 70–90% and < 50%, respectively [3,4,5,6,7,8]
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