Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with
malignant hernatological disorders during disease progression. We
describe a 50-year-old male patient who had originally presented
with pancytopenia in October 1992. The diagnosis of a
myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established
in April 1993 by histological bone marrow (BM) examination, and
therapy with low-dose cytosine arabinoside was initiated. In a
phase of partial hernatological remission, cytogenetic assessment
in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases
beside BM cells with normal karyotypes
{[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient
progressed to an acute myeloid leukemia (AML), subtype M4 with 40%
BM blasts and cytogenetic examination showed clonal evolution by
the appearance of additional numerical aberrations in addition to
the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46,
XY]. Intensive chemotherapy and radiotherapy was applied to induce
remission in preparation for allogeneic bone marrow transplantation
(BMT) from the patient's HLA-compatible son. After BMT, complete
remission was clinically, hematologically and cytogenetically
(normal male karyotype) confirmed. A complete hematopoietic
chimerism was demonstrated. A relapse in January 1997 was
successfully treated using donor lymphocyte infusion and donor
peripheral blood stem cells (PB-SC) in combination with GM-CSF as
immunostimulating agent in April 1997, and the patient's clinical
condition remained stable as of January 2005. This is an
interesting case of a patient with AML secondary to MDS. With the
ring chromosome 1 we also describe a rare cytogenetic abnormality
that predicted the poor prognosis of the patient, but the patient
could be cured by adoptive immunotherapy and the application of
donor's PB-SC. This case confirms the value of cytogenetic analysis
in characterizing the malignant clone in hernatological neoplasias,
the importance of controlling the quality of an induced remission
and of the detection of a progress of the disease. Copyright (c)
2006 S. Karger AG, Basel.