Traumatic Lumbar Puncture (TLP) Is Not Associated with Worse Outcome in Adults with Acute Lymphocytic Leukemia (ALL) or Burkitt-Type Leukemia/Lymphoma (BLL) Receiving Hyper-CVAD Regimens.

Background: TLP has been associated with worse outcome in pediatric ALL patients (pts). However, this has not been well studied in adults with ALL or BLL. Our aim was to investigate the prognostic significance of CNS status at presentation in adult ALL pts undergoing frontline therapy with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine) or variations incorporating rituximab and/or imatinib. Pts were stratified to receive standard intrathecal treatments (IT) with methotrexate alternating with cytarabine based on CNS risk assessment (proliferative index ≥ 14% or serum lactate dehydrogenase ≥ 1400) [Cortes et al, Blood 86:2091, 1995]. Low risk pts received 6 IT, high or indeterminate risk 8 IT, and BLL 16 IT.

Methods and Results: Cerebrospinal fluid was assessed after IT approximately day 2 of induction therapy. CNS status at presentation was defined as: CNS 1 (not traumatic; < 10 RBCs/μL without leukemic blasts after cytocentrifugation); CNS 2 (not traumatic; < 5 WBCs/μL with leukemic blasts); CNS 3 (not traumatic; ≥ 5 WBCs/μL with leukemic blasts), TLP+ (traumatic, > 10 RBCs/μL with leukemic blasts). TLP- (traumatic without leukemic blasts). Two hundred eighty two pts were reviewed up to January 2007; the median age was 42 years (range, 15–84). Diagnosis was ALL in 229 (81%) and BLL in 53 (19%). In the ALL subset, 48 pts (17%) were Philadelphia positive. Median WBC and platelet count were 3.2 x 10⁹/L and 65 x 10⁹/L, respectively. At the time of first LP, 119 (42%) pts had circulating (PB) blasts. CNS risk was high in 34% (plus 17% with BLL), indeterminate in 20%, and low in 21%. The remainder (7%) had definitive CNS disease and were not classified. PB blasts and CNS risk did not appear to affect the CNS relapse rate. By multivariate analysis, age, thrombocytopenia, leukocytosis and presence of t(4;11) were associated with worse survival in this selected group, while CNS status at presentation was not (Table 1).

Conclusion: CNS status at first LP does not appear to affect prognosis of adults with de novo ALL or BLL receiving frontline therapy with hyper-CVAD based regimens. TLP or the presence of PB blasts at the time of first LP does not appear to increase the risk of CNS relapse.