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Kinetics of minimal residual disease during induction/consolidation therapy in standard-risk adult B-lineage acute lymphoblastic leukemia.

Abstract：

:We have compared the kinetics of minimal residual disease (MRD) by simultaneous polymerase chain reaction (PCR) monitoring with oligonucleotides for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 (CDR3) and the T-cell receptor gamma chain gene (TCR gamma), as well as clone-specific CDR3 sequences in adult patients (aged 17-51 years) with acute lymphoblastic leukemia (ALL) who entered a complete hematological remission (CR) after chemotherapy with the German multicenter ALL (GMALL) protocol. The sensitivities were one in 10(2-3) for the CDR3- and TCR gamma-PCR and one in 10(5-6) for a two-step, seminested CDR3/clone-specific PCR. At diagnosis, 7/7 patients were CDR3 positive and four were TCR gamma positive in their bone marrow (BM). At the end of induction therapy (after 2 months) 4/6 tested positive for CDR3, 2/6 for TCR gamma, and 5/6 for clone-specific rearrangements. At the end of consolidation treatment (after 7 months) only 1/7 remained positive for CDR3, 2/7 for TCR gamma, and 5/7 for clone-specific rearrangements. After an observation period of 18-36 months, 4/7 patients were still in CR and all were PCR negative by the clone-specific method during or after maintenance therapy. Two patients died in leukemic relapse; one patient relapsed but is still alive. All three of these patients remained PCR positive throughout the course of their disease. Clonal evolution in the IgH locus was found in one of these patients. We conclude that the molecular response to chemotherapy in adult B-lineage ALL is slow, even in patients without risk factors other than age. As in childhood ALL, most patients with long-term CR convert to PCR negativity approximately 18 months after the start of chemotherapy. The data also suggest the existence of early clone-specific PCR negativity in a small proportion of long-term survivors. The predictive value of this observation will now have to be confirmed in a larger study.

journal_name

Ann Hematol

journal_title

Annals of hematology

authors

Scholten C,Födinger M,Mitterbauer M,Laczika K,Mitterbauer G,Haas OA,Knöbl P,Schwarzinger I,Thalhammer R,Purtscher B

doi

10.1007/BF01910311

subject

Has Abstract,Author List Incomplete

pub_date

1995-10-01 00:00:00

pages

155-60

issue

eissn

0939-5555

issn

1432-0584

journal_volume

pub_type

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Kinetics of minimal residual disease during induction/consolidation therapy in standard-risk adult B-lineage acute lymphoblastic leukemia.