Unusual extramedullary relapse of CML

The treatment of chronic myelogenous leukemia (CML) has been revolutionized by the advent of imatinib, a specific tyrosine kinase inhibitor. Imatinib has proven its superiority over the combination of interferon-{alpha} (IFN-{alpha}) and cytarabine in yielding both cytogenetic and molecular remissions [1Go]. However, clinical manifestations of relapse have not yet been defined in individuals receiving imatinib because of its recent introduction to clinical practice.

We report the case of a 49-year-old man who was diagnosed with chronic-phase CML in September 1999, and treated for 9 months with IFN-{alpha} and cytarabine without cytogenetic response. Imatinib 600 mg p.o. o.d. was initiated in July 2000 and resulted in complete hematologic, cytogenetic and molecular remission, which was documented initially in August 2001. In November 2003, he disclosed a 10-month history of worsening left buttock pain. Physical examination revealed left inguinal lymphadenopathy and a soft tissue mass in the left iliac region. Computerized axial tomography of the abdomen and pelvis demonstrated a 9 cm mass destroying the left iliac wing, as well as left iliac lymphadenopathy (Figure 1). Biopsy of a left inguinal lymph node and of the left iliac soft tissue mass revealed CD34-positive myeloblasts. Fluorescent in situ hybridization of the iliac bone specimen identified major BCR/ABL b3a2 type consistent with extramedullary relapse of CML in myeloid blast phase. Surprisingly, there was no hematologic or cytogenetic evidence of relapse in a bone marrow sample obtained from the right posterior iliac crest, and peripheral blood was negative for BCR/ABL according to polymerase chain reaction.



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Figure 1. Soft tissue mass destroying left iliac bone.

 
There have been no reported cases of isolated extramedullary relapse of CML in individuals who have achieved a molecular remission with imatinib. Such relapses have also only rarely been seen with allogeneic stem cell transplantation, another modality capable of inducing a molecular remission in CML [2Go–4Go]. Our patient's late relapse at unusual sites could have been overlooked because the results of tests normally employed to confirm molecular and cytogenetic remission in CML were still entirely negative. It is possible that with longer follow-up, more patients with CML achieving molecular remission with imatinib will relapse at unusual sites. Therefore, it behooves physicians utilizing imatinib for the treatment of CML to remain vigilant with respect to unusual signs and symptoms.

A. Smaradottir1,*, D. Kapur2 and S. Bilgrami3

1 University of Connecticut Health Center, Farmington, CT 06030; 2 Eastern Connecticut Hematology/Oncology Associates Norwich, CT 06360; 3 St Francis Hospital and Medical Center, Hartford, CT 06105, USA

* Email: smaradottir{at}gme.uchc.edu

References

1. O'Brien SG, Guilhot F, Larson RA et al. Imatinib compared with interferon and low dose cytarabine for newly diagnosed chronic phase chronic myeloid leukemia. N Engl J Med 2003; 348: 994–1004.[Abstract/Free Full Text]

2. Au WY, Chan AC, Lie AK et al. Isolated extramedullary relapse after allogeneic bone marrow transplantation for chronic myeloid leukaemia. Bone Marrow Transplant 1998; 22: 99–102.[CrossRef][ISI][Medline]

3. Martel L, Reddy K, Greco M et al. Isolated cavernous sinus extramedullary relapse of chronic myelogenous leukaemia following allogeneic stem cell transplant. Ann Hematol 2002; 81: 108–110.[CrossRef][ISI][Medline]

4. Kroschinsky F, Friedrich K, Hanel M et al. Extramedullary blast crisis of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation mimicking aggressive translocation t(14;18)-positive B-cell lymphoma. Ann Hematol 2003; 82: 47–52.[ISI][Medline]