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Lenalidomide therapy in del(5)(q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions

Leukemia volume 21, pages 1827–1828 (2007)Cite this article

Lenalidomide (CC-5013; Revlimid) is structurally related to thalidomide but belongs to a new line of immunomodulatory drugs (IMiDs) with a more potent anti-angiogenic and anti-inflammatory activity that is mediated by pleiotropic cytokine regulation. Among myeloid neoplasms, the most impressive treatment results with lenalidomide have been reported in del(5)(q31)-associated myelodysplastic syndrome (MDS) – 45% complete cytogenetic response and an even higher rate of hematologic response.1 Less impressive but notable hematologic response rates have also been documented in MDS without del(5q)2 and primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF) myelofibrosis.3 Most recently, two single case studies reported lenalidomide-induced response in del(5q)-associated acute myeloid leukemia (AML).4, 5 Herein we describe a similarly positive experience with lenalidomide therapy in three consecutive patients with del(5q)-associated PMF or post-PV MF (all three patients were JAK2V617F-positive); the report includes two new cases and follow-up information on a previously described patient.3 Bone marrow histology in all instances was re-reviewed by two of the authors (AT and CAH) to confirm the diagnosis of PMF or post-PV MF as opposed to MDS with bone marrow fibrosis. Del(5)(q) was assessed by both conventional cytogenetics and fluorescent in situ hybridization (FISH) using probes for 5p15.2 (D5S23, D5S721) and 5q31 (EGR1). Quantitative allele-specific PCR was utilized for JAK2V617F mutation screening.6 Clinical and laboratory parameters at baseline and post-lenalidomide treatment are presented in Table 1.

Table 1 Baseline and post-treatment clinical and laboratory features of three patients with del(5)(q31)-associated primary myelofibrosis (PMF) or post-polycythemia vera myelofibrosis (post-PV MF)
Full size table

Case 1 was a 75-year-old man with post-PV MF who was chemotherapy naïve before starting lenalidomide therapy (10 mg/day). At baseline, the patient displayed del(5)(q13q33) in all metaphases. After 3 months of side effect-free treatment with lenalidomide the complete blood count and peripheral blood smear normalized; hemoglobin improved from 9.4 to 14.2 g/dl, platelet count from 831 to 156 × 109/l, and leukoerythroblastosis was no longer present. Bone marrow biopsy disclosed complete resolution of hypercellularity, abnormal megakaryopoiesis, and myelofibrosis. Cytogenetic studies revealed 29 normal metaphases and one metaphase with del(5)(q); FISH for del(5)(q) was within normal limits. At 6 months, a complete cytogenetic remission was achieved both by karyotype and FISH; the percentage of abnormal nuclei by FISH decreased from 78 to 0%. At 9 months, JAK2V617F allele burden in bone marrow-derived DNA had decreased from the baseline of 4 to <1%. Although lenalidomide was discontinued after 6 months of therapy, because of protocol requirement, the patient remained in hematologic remission for an additional 12 months (that is a total of 15 months) before he relapsed with acute erythroid leukemia (AML M6); cytogenetic studies revealed eight abnormal metaphases with del(5)(q13q33) and other complex anomalies and JAK2V617F had reappeared. The patient did not respond to lenalidomide re-treatment.

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  1. Division of Hematology and Laboratories of Cytogenetics, Mayo Clinic, Rochester, MN, USA

    A Tefferi, T L Lasho, R A Mesa, A Pardanani & R P Ketterling

  2. Division of Hematopathology, Mayo Clinic, Rochester, MN, USA

    C A Hanson

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  1. A Tefferi
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Correspondence to A Tefferi.

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Tefferi, A., Lasho, T., Mesa, R. et al. Lenalidomide therapy in del(5)(q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions. Leukemia 21, 1827–1828 (2007). https://doi.org/10.1038/sj.leu.2404711

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