CD34 is a member of the trans-membrane sialomucin proteins expressed on the surface of hematopoietic cells and plays an important role as a cell-cell adhesion factor and mediates attachment of stem cells to extracellular matrix. Clinically, CD34 and other surface markers, such as CD13 and CD33, are frequently used as differentiation markers: CD34 for stem cells and CD13 and CD33 for myeloid differentiation. CD34 is not expressed on the surface of leukemic cells in a significant number of patients with acute lymphoblastic leukemia (ALL). CD13 and CD33 are expressed on the surface of lymphoblasts in few ALL patients. The clinical significance of CD13 and CD33 expression on the surface of lymphoblasts in ALL has been studied extensively in patients treated with conventional chemotherapy. The clinical relevance of the expression of CD34, CD13 and CD33 on outcome in ALL patients treated with allogeneic hematopoietic stem cell transplant (HSCT) is not known. We studied the prognostic relevance of the expression of CD34, CD13, and CD33 on outcome of adult ALL patients when treated with allogeneic HSCT, either in the first remission or after relapsing and correlated the expression with outcome.
Data collected from immunophenotyping of 62 patients with ALL who were treated with HSCT was reviewed and the expression of the CD34, CD13, and CD33 on the blast population as determined using flow cytometry was correlated with clinical behavior and outcome. Thirty-eight (61%) of these patients were treated with HSCT in first remission (CR1), while the rest of the patients were transplanted in the second or third remission. The median age of these patients was 19 (range: 14–43) and included 17 females (27%) and 45 males (73%). Cytogenetics at diagnosis classified the patients as intermediate in 24 cases (39%), adverse in 31 (50%), and favorable in 5 (8%). Cytogenetic data was not available on two patients.
Twenty-four (39%) of all patients did not express CD34 on the surface of the blasts at diagnosis, while 13 (21%) patients expressed CD13 and 19 (31%) expressed CD33. ALL patients who did not express CD34 had significantly shorter overall survival (OS) (P=0.003) and event free survival (EFS) (P=0.009). However, when only patients who were treated with HSCT in CR2 or CR3 were considered, CD34 expression was not relevant for OS or for EFS. Patients treated with HSCT in CR1 had significantly better OS (P=0.00) and EFS (P=0.00) if they expressed CD34. In contrast, expression of CD13 or CD33 had no impact on OS or EFS.
Our data suggests that CD34 expression, and not CD13 or CD33, has a favorable impact on overall survival as well as EFS in adult ALL patients being treated with HSCT in CR1, however it loses its prognostic relevance in patients transplanted in more advanced disease.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.