The significance of persistance of clonal cells post-induction in the marrow of pediatric patients with all

Jukka Kanerva, Kirn Vettenranta, Wael El-Rifai

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Abstract

The evaluation of minimal residual disease (MRD) is increasingly gaining ground in the prognostic assessment and attempted tailoring of therapy of childhood ALL. We prospectively studied MRD by metaphase FISH in 42 children (21 males) with newly diagnosed ALL; 35 precursor B, 6 T-ALL, and one with incomplete immunophenotyping. All children were treated according to the NOPHO-92 protocol. At diagnosis all patients were karyotyped by standard G-banding as well as studied with comparative genomic hybridization. Standard cytogenetic preparations were used for FISH. Ten of the 42 children were FISH-positive at some point post-induction. One of these had a bone marrow relapse at cessation of therapy, the other remain in CCR. Four of the 10 FISH-positive were positive also after cessation of therapy, but none have thus far relapsed (median follow-up 27 mos). Of the the 32 children with no FISH-detectable MRD post-induction, three have relapsed. Metaphase-riSH results of 10 patients with MRD post-induction 1 3 6 9 12 15 18 2] 24 27 30 33 36 1 f..Q..........g.......... ............................................. .........R 2 o- -.-0- -..............................o-O 3 ..."o-....... ......................................o-.... ...-d-.........................| 4....................... ..............o............................................o|.......O-.-0-.-0-.. -O =43 5...........................................O................. -o-OlO.OO-O-OO- -.0 .-..-O =42 6 o...-.-.-.....-.-0-................................0.-.......-..Ol 7 .............................. ............o............ ..........................................It-O.O-O.- O 420 48 8............................................................... ......................f |......................Q.-O-O = 49 9 O-0-.-.-..-.-..-.-.-O-..-l .....o- -O 10-. .............................0 -....-o- O-O 0 o- -ol-.0-O-O- -0- -. -0 = 48 3 6 9 12 15 18 21 24 27 30 33 36 Months from diagnosis O negativ positive I end of therapy R relapse We show that despite of the presence of mitotically active blasts from the original leukemic clone during or after treatment, most of the children remain in continuous hematological remission although no action is taken to intensify or prolong the treatment. With several methods (PCR, FACS, FISH) available for monitoring MRD, the role of each of these or their combinations in the prognostic assessment or individualization of therapy in childhood ALL remain to be elucidated.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART II
StatePublished - Dec 1 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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