Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: Results from a sequential treatment CLL protocol Journal Article


Authors: Noy, A.; Verma, R.; Glenn, M.; Maslak, P.; Rahman, Z. U.; Keenan, J. R.; Weiss, M.; Filippa, D.; Zelenetz, A. D.
Article Title: Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: Results from a sequential treatment CLL protocol
Abstract: Patient-tumor-specific oligonucleotides were generated for the detection of minimal residual disease (MRD) in a highly specific and sensitive clonotypic polymerase chain reaction (cPCR). The clone-specific region of highest diversity, CDR-III, was PCR amplified and sequenced. Nested CDR-III clonotypic primers were used in a semi-nested cPCR with a sensitivity of at least 1 in 105 cells. Patients with protocol-eligible Rai intermediate or high-risk chronic lymphocytic leukemia (CLL) received induction with fludarabine 25 mg/m2 per day for 5 days every 4 weeks for 6 cycles, followed by consolida tive high-dose cyclophosphamide (1.5, 2.25, or 3g/m2). cPCR was performed on peripheral blood and bone marrow mononuclear cells. All 5 patients achieving a clinical partial remission (PR) studied by cPCR were positive. Five patients achieved nodular PR (nPR) (residual nodules or suspicious lymphocytic infiltrates in a bone marrow biopsy as the sole suggestion of residual disease). Five of 5 patients with nPR were CPCR positive. In contrast, flow cytometry for CD5-CD19 dual staining and κ-λ clonal excess detected MRD in only 3 of the same 5 nPR patients, all of whom were CPCR positive, and immunohistochemistry detected MRD in only 1 of 4 assessable patients. Three of 7 CR patients evaluable by cPCR had MRD. Only 1 CR patient had MRD by flow cytometry; that patient was also cPCR positive. These data support the conclusions that nodular PR in CLL represents MRD and that clonotypic PCR detects MRD in CLL more frequently than flow cytometry or immunohistochemistry. ¢ 2001 by The American Society of Hematology.
Keywords: immunohistochemistry; clinical article; treatment outcome; human cell; fludarabine; flow cytometry; lymph nodes; diagnostic accuracy; sensitivity and specificity; polymerase chain reaction; bone marrow; antineoplastic combined chemotherapy protocols; neoplasm proteins; tumor markers, biological; cyclophosphamide; molecular cloning; cancer regression; dna; gene rearrangement; immunoglobulin heavy chains; minimal residual disease; neoplasm, residual; remission induction; antigens, cd; chronic lymphatic leukemia; immunoglobulin kappa-chains; immunoglobulin lambda-chains; oligonucleotide; clone cells; dna determination; vidarabine; leukemia, lymphocytic, chronic; genes, immunoglobulin; leukemic infiltration; gene rearrangement, b-lymphocyte, heavy chain; human; priority journal; article
Journal Title: Blood
Volume: 97
Issue: 7
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2001-04-01
Start Page: 1929
End Page: 1936
Language: English
DOI: 10.1182/blood.V97.7.1929
PUBMED: 11264154
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
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Citation Impact
MSK Authors
  1. Ariela Noy
    278 Noy
  2. Andrew D Zelenetz
    647 Zelenetz
  3. Peter Maslak
    191 Maslak
  4. Mark Weiss
    86 Weiss
  5. Daniel A Filippa
    145 Filippa
  6. James R Keenan
    3 Keenan