A Retrospective Analysis of Myeloproliferative Neoplasms: Treatment Approach and Outcomes at Drexel University Hospital

BACKGROUND

Myeloproliferative neoplasms (MPN) are a group of clonal disorders that arise from a transformation in a hematopoietic stem cell. These disorders consist of chronic myeloid leukemia (CML), essential thrombocytosis (ET), primary myelofibrosis (PMF) and polycythemia vera (PCV). Several therapeutic agents have been used in the past to treat these disorders. Treatment strategies for these patients must consider the possibility of long-term survival, morbidity from thrombotic complications, transformation into myelofibrosis with myeloid metaplasia or acute myeloid leukemia, and the effect of specific therapies on the incidence of leukemic transformation and on pregnancy. At Drexel University, a significant number of patients were treated with busulfan and were thought to have a more favorable clinical course and increased survival in comparison to other agents. Due to the perceived side effects associated with busulfan, the current preferred cytoreductive agent is hydroxyurea. In our study we analyzed the outcomes of patients treated in the practice of I. Brodsky Associates diagnosed with ET, PCV and PMF, who received a variety of treatment modalities, and compared their clinical courses to determine if there is a superior treatment.

METHODS

This study is a retrospective cohort study in which we have examined the medical records of patients treated for the diagnoses of ET, PCV and PMF at Hahnemann Hospital-Drexel University College Medicine in the practice of I. Brodsky Associates from January 1960 to December 2013. The following variables were measured and compared: age at diagnosis; sex; race; cytogenetics; family history of malignancy; baseline hemoglobin, hematocrit, platelet count and WBC count; Bone marrow biopsy results; thrombohemorrhagic complications; transformation to acute leukemia, progression to myelofibrosis; development of secondary malignancies; and treatment. Since the diagnostic criteria for myeloproliferative disorders has evolved over the years, information regarding JAK2 V617F mutation status, initial erythropoietin level, red cell mass, oxygen saturation, presence of splenomegaly and B12 level were also collected in order to confirm the diagnosis of each patient. The treatment categories analyzed were: Busulfan Only, Hydroxyurea Only, Aspirin with or without Plavix only, Both Busulfan and Hydroxyurea, and Phlebotomy Alone. The forms were then analyzed using Prism software and the number of observations, percentages, means, standard deviation, and minimum and maximum values were obtained for all measurements. Survival was calculated using Kaplan-Meier analysis.

RESULTS

119 patients with a MPN were identified: 47 ET, 56 PCV, 8 PMF and 7 MPN NOS. Median ages were 70, 75, 63 and 67, respectively. 34 received Busulfan, 26 Hydroxyurea, 24 Busulfan and hydroxyurea, 24 Aspirin/Plavix only, 11 phlebotomy; one patient who was given Interferon and Aspirin was excluded from analysis.

Malignancies noted: Pancreatic cancer (4), Breast cancer (4), and Non-Hodgkin's lymphoma (3). Basal and squamous cell skin cancers were excluded.

CONCLUSIONS

MPN have been treated in much the same way for many years although few physicians use busulfan as routinely as I. Brodsky Associates. Our study set out to discover if this uncommon treatment correlated with improved survival and less treatment toxicity. Busulfan and hydroxyurea given together proved to have the lowest rate of progression to leukemia or myelofibrosis when compared to other standard therapies. The median survival of patients treated with both busulfan and hydroxyurea was 14.8 years. More patients on busulfan developed solid tumors, which could be possibly due to their longer survival rates, but increased leukemic transformation was not observed. In conclusion, patients treated with hydroxyurea and intermittent busulfan, were shown to have the best long-term outcomes. This suggests that physicians should consider using busulfan to treat MPNs.