¹Section on Hematology and Oncology, Comprehensive Cancer Center at Wake Forest University, Winston-Salem, NC, USA

Correspondence: Y-K Keung, Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Medical Center Boulevard, Winston-Salem, NC, USA. Fax: +1 336 716 5687; E-mail: ykeung@wfubmc.edu

Received 18 November 2003; Accepted 9 December 2003; Published online 12 February 2004.

TO THE EDITOR

We read with interest the paper by Ruchatz et al¹ on the effect of imatinib on hematopoietic recovery following idarubicin exposure in murine model. We describe an elderly patient with chronic myeloid leukemia (CML) and transformed large B-cell lymphoma treated with imatinib mesylate and combination chemotherapy.

This is an 87-year-old male with a history of follicular lymphoma involving left cervical nodes in 1996, and he refused further therapy. He presented again in July 2000 with a markedly elevated WBC of 223 000/l. A bone marrow examination confirmed the diagnosis of CML in chronic phase with cytogenetic study showing 45X,-Y,t(9; 22)(q34; q11)[25]. He was initially started on hydroxyurea and subsequently anagrelide was added because of thrombocytosis. In November 2001, the therapy was switched to imatinib mesylate when it was available commercially. At the same time, he started to experience nasal congestion and difficulty in swallowing. Both ENT evaluation and CT imaging demonstrated a large nasopharyngeal mass with biopsy confirming the presence of CD20-positive, diffuse large B-cell lymphoma probably transformed from the preceding follicular lymphoma. He received a cycle of CHOP chemotherapy, consisting of cyclophosphamide, adriamycin, vincristine and prednisone at 80% of the normal dosage, on 9 January 2002 concomitant with imatinib, and it resulted in prolonged neutropenia (Figure 1). Imatinib was discontinued and eventually local radiation therapy was given instead. After completion of radiation, imatinib was restarted on 15 March 2002 with the daily dosage of imatinib adjusted to 300 mg per day based on the white blood counts. CT imaging in April 2002 revealed complete resolution of the nasopharyngeal mass. In January 2003, his peripheral blood was negative for BCR-ABL gene rearrangement by polymerase chain reaction. Unfortunately, his disease relapsed locally in February 2003. In view of the previous history of prolonged pancytopenia, the imatinib was discontinued and attenuated Rituxan-CHOP at 67% normal dosage was started. He tolerated the chemotherapy well with prompt marrow recovery and went on to receive second and third cycles of Rituxan-CHOP at 80 and 90% normal dosage, respectively, every 3 weeks. Subsequent CT scans in April 2003 again revealed complete resolution of the nasopharyngeal mass. Owing to the patient's advanced age and concomitant diagnosis of CML, the chemotherapy was discontinued as per the family's request. He was restarted on imatinib 300 mg/day in April 2003 when the peripheral blood turned positive for BCR-ABL. His nasopharyngeal disease again progressed in July 2003 and Rituxan-CHOP at 67% was restarted with him continuing on imatinib. However, the patient developed prolonged pancytopenia and the imatinib was promptly discontinued. His next course of chemotherapy was given in 5-week cycle instead of the usual 3-week cycle. Without concomitant imatinib, his subsequent courses of chemotherapy were successfully given every 3 weeks and with dose escalation (Figure 2) without the side effects.

Figure 1.

Delayed hematopoietic recovery after first course of CHOP chemotherapy.

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Figure 2.

Improved hematopoietic recovery after discontinuation of imatinib.

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Our case supports the finding of Ruchatz et al and suggests that caution be exercised when imatinib is to be used in combination with systemic chemotherapy.