Uncommon long-term survival in a patient with chronic myeloid leukemia

To the Editor

The introduction of Imatinib Mesylate (IM) has revolutionized the treatment of patients with Chronic Myeloid Leukemia (CML) in chronic phase (CP), resulting in high rates of hematologic, cytogenetic and molecular responses [1]. Clinical evidence estimates 89% of overall survival (OS) at 60 months for patients receiving IM on an intention to treat basis [2]. Before the advent of IM, conventional cytotoxic chemotherapy had failed to cure CML and standard treatment for CP-CML was alpha-interpheron (IFN), which demonstrated an OS at 10 years of 20–53% [3]. On this basis, CML clinical progression to a fatal blast crisis was inevitable [4] and long-term survival in patients with CML extremely unusual. Here we report the case of a patient with CML that represents, to the best of our knowledge, one of the longest survivors described so far in the literature.

A 47-year-old female was referred to a civic hospital in 1986 because of fever and leukocytosis and was diagnosed with CP-CML. She was started with Busulphan (BU) therapy (at conventional doses) as first line treatment, achieving a complete hematological response (CHR) within two months. The patient, in CHR and overall good clinical standing, was maintained in follow-up without further treatment. During this period of time, the white blood cell (WBC) count was normal and the spleen was not enlarged. In December 1997 she lost her CHR, presenting with leukocytosis (WBC 25.000/ mmc). She was then retreated with BU for five months obtaining a second CHR. In January 2004, the patient again displayed high WBC counts (21.000/ mmc) and mild hepato-splenomegaly and was referred to our Institution. Bone marrow cytogenetic analysis showed 96% Philadelphia-positive (Ph + ) cells with no evidence of other abnormalities while molecular analysis revealed a BCR-ABL/ABL ratio of 31.3% on the International Standardized Scale (IS). She was classified as having CP-CML, low Sokal risk and therefore commenced IM 400 mg/day obtaining an early CHR. After 12 months of treatment, she achieved a CCyR and her BCR-ABL/ABL ratio decreased to 0.13%. At 24 months of therapy, the patient displayed both a CCyR and a MMR (BCR-ABL/ABL transcript 0.038%^IS). She is presently alive and well and still on standard IM therapy, maintaining both CCyR and MMR.

CML treated with both BU and Hydroxyurea was invariably associated with a poor prognosis [5]. Even though these agents were able to control the hematological manifestations of the disease, they seldomly delayed CML progression. Here we report a CML patient with CP-disease duration and overall survival of over 22 years. To the best of our knowledge, this patient is one of the longest survivors among CML patients that were not initially treated with either IFN or IM. We have found only two other cases in the literature with a similar unusually long survival [6], [7]. All these patients presented low Sokal risk and high sensitivity to standard doses of BU with modest treatment-induced toxicities (in our patient we failed to observe BU-dependent myelosuppression or bone marrow hypoplasia). These unusually long survivals might reflect lower rates of genomic instability in the leukemia-initiating cell or simply the occurrence of the Ph chromosome in a more differentiated progenitor. In this biological context, although unable to eradicate the leukemic clone, BU-treatment seems extremely effective in reducing the proliferative and anti-apoptotic signaling of the CML-originating cell, possibly playing a role in the long overall survival of these patients.