Case 368

Submitting Author: Kovarik, Paula, MD
Institution: John H. Stroger Jr. Hospital of Cook Countyh
Additional authors:Shivi Jain, Rosalind Catchatourina
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN

HISTORY

Male patient diagnosed with chronic myelogenous leukemia (CML) at age 55 in 2002 in Mexico. He was started on hydroxyurea. He moved to US shortly thereafter and was treated with Ara-C/Interferon. He came to our hospital in 2003 and was started on imatinib mesylate 400 mg/day. He developed pancytopenia, rectal abscess and intravenous port infection. His does of imatinib was decreased 200 mg/day.

In 2005 he went to Mexico. His compliance with imatiib was unknown during his time there. In 2006 he developed anemia with macrocytosis with normal B12 and folate levels. He received erythropoietin injections. The imatinib was stopped for 6 weeks and his CBC recovered. He again went to Mexico and his compliance with imatinib was again unknown during his time there.

In 2009 he was noted to have thrombocytopenia and anemia and 4% blasts in his peripheral blood. Bone marrow was hypercellular with dysplastic changes. In June 2009 he was treated with azacitidine. He developed a significant transfusion requirement and showed no response to therapy.

In February 2010 he developed CNS involvement and was given intrathecal ARA-C and cranial irradiation. He was also started on induction chemotherapy for acute myelogenous leukemia. Repeat bone marrow was demonstrated chronic phase CML. He did not respond to additional treatment and died in May 2010.

DETAILS

April 2009 - bone marrow performed. Formalin-fixed marrow biopsy is hypercellular with increased reiculin. Aspirate was a dry tap. Tough preparations of the biopsy showed 11% blasts with dysplastic changes in megakaryocytes and erythroid precursors. Peripheral blood showed 8% blasts.

April 2010 - bone marrow performed. Formalin-fixed bone marrow biopsy is hypercellular with granulocytic predominance. No increase in blasts.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

April 2009 - flow cytometry of material obtained during the bone marrow aspirate (no spicules present) identified a myeloid blast population which showed co-expression of CD33, CD34, and HLA-DR.

April 2010 - flow cytometry of bone marrow aspirate did not identify abnormal populations

CYTOGENETIC FINDINGS

2009 - bone marrow karyotype 45,X,?inv(Y)(p11.2;q12),-7 in all cells examined.

2010 - bone marrow karyotype 46,XY,t(9;22)(q34;q11.2)[18]/45,X,inv(Y)(p11.2;q12),-7[3].

MOLECULAR FINDINGS

2009 - FISH study demonstrated bone marrow monosomy 7.

2010 - FISH study demonstrated BCR/ABL 1 gene rearrangement in 88.8% of interphase nuclei examined.

INTERESTING FEATURES

Development of myelodysplastic syndrome following imatinib mesylate therapy. Clinical disease progression to involve CNS. Treatment showed reversion to chronic phase CML with persistence of MDS clone.

PROPOSED DIAGNOSIS

Myelodysplastic syndrome following imatinib mesylate therapy.

CONSENSUS DIAGNOSIS

Myelodysplastic syndrome arising in a patient with chronic myelogenous leukemia, BCR-ABL1 positive, treated with tyrosine kinase inhibitor therapy (imatinib)