Leukemia & Lymphoma, June 2011; 52(S2): 62–64
Definition of remission, minimal residual disease, and relapse in hairy cell leukemia bone marrow biopsy histology and immunohistology specimens
PIERRE NOEL Division of Hematology-Oncology and Department of Laboratory Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA
Abstract No consensus has been reached in the definitions of complete remission (CR) and minimal residual disease (MRD) on bone marrow biopsy specimens of patients with hairy cell leukemia (HCL). Large comparative studies correlating clinical outcome with detection of MRD by immunohistochemistry (IHC), flow cytometry, and molecular diagnostics are lacking. The presence of normal bone marrow B-lymphocytes and the lack of immunohistochemical stains that are both sensitive and specific can make it challenging to differentiate normal lymphocytes from hairy cells. The use of CD20 and/or DBA.44 immunohistochemical stains, in combination with either tartrate resistant acid phosphatase (TRAP), CD11c-5D11, or annexin A1, improve specificity and facilitate evaluation. The interobserver concordance in quantifying the percentage of residual hairy cells is poor. Performing cell counts in multiple fields improves reproducibility. The prolonged hematologic remissions of subsets of patients with MRD emphasize the need to define clinically relevant thresholds that correlate with long-term responses and clinical endpoints. The development of internationally accepted, reproducible, and clinically relevant CR, MRD, and relapse criteria are of paramount importance in evaluating and comparing clinical trials and in providing optimal patient care.
Keywords: Lymphoid leukaemia, minimal residual disease
There is no consensus in defining remission, minimal residual disease, and relapse in bone marrow biopsy specimens. The criteria used in National Cancer Institute intramural protocols combine clinical and bone marrow histological and immunohistological findings [1]. Complete remission (CR) requires absence of hairy cell leukemia (HCL) in blood and bone marrow using non-immunological stains, non- palpable spleen, and/or negative computed tomogra- phy, and resolution of cytopenias. Minimal residual disease (MRD) in the bone marrow requires: (1)
CD20-positive cells CD3-positive cells, (2) tartrate resistant acid phosphatase (TRAP)-positive cells consistent with HCL, and (3) more than 50% of the CD20-positive cells morphologically consistent with
HCL. Partial remission requires 50% reduction in tumor burden and improvement in cytopenias to
hematologic remission levels, or 50% improvement in baseline neutrophils, platelets, and hemoglobin. Ravandi et al. [2] define CR as the absence of hairy
cells on bone marrow aspirate smears or the presence of fewer than 1% atypical cells (not definitely called
hairy cells) in bone marrow and blood and the disappearance of all evidence of HCL on physical examination. Achievement of CR requires an abso- lute neutrophil count (ANC) of at least 1.56109/L; hemoglobin (Hgb) at least 120 g/L (at least 110 g/L for women); and platelet count at least 1006109/L without growth factor or transfusion support. CR with residual disease is defined as for CR but with persistence of 1–5% hairy cells in the marrow (but no circulating hairy cells). Partial remission is defined as: (1) meeting the peripheral blood criteria for CR/ complete remission with residual disease (CR-RD) but more than 5% residual hairy cells in the marrow, or (2) at least 50% improvement or correction of at least one cytopenia without a decrease in any other cell count, reduction in palpable abnormalities on physical examination by at least 50%, and reduction in circulating or bone marrow hairy cells by at least 50%. Ellison et al. [3] defined MRD as five cells with morphologic features of hairy cells and with positivity for CD20 and/or DBA.44.
Correspondence: Pierre Noel, MD, Mayo Arizona, Hematology, 13400 East Shea Blvd, Scottsdale, 85259 United States. E-mail:
Pierre.Noel@
mayo.edu
ISSN 1042-8194 print/ISSN 1029-2403 online 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2011.565098
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