Busulphan is safe and efficient treatment in elderly patients with essential thrombocythemia

Shvidel, Lev; Sigler, Erica; Haran, Michal; Klepfish, Abraham; Duek, Adrian; Berrébi, Alain; Shtalrid, Mordechai

doi:10.1038/sj.leu.2404743

Cited by 47 publications

(29 citation statements)

References 6 publications

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“…These figures were well within the baseline risk that is intrinsic to the diseases and no different than those seen with hydroxyurea [115]. The safety and efficacy of busulfan treatment in ET was recently underlined by a long-term study of 36 patients above age 60 years of age [116]; no instances of AML or other malignancies were documented after a median followup of 72 months. In a more recent study of over 1,500 patients with PV, use of busulfan was not correlated with leukemic transformation [50].…”

Section: Annual Clinical Updates In Hematological Malignanciesmentioning

confidence: 66%

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

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Disease overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms, respectively characterized by erythrocytosis and thrombocytosis. Other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: PV is defined by a JAK2 mutation, whose absence, combined with normal or increased serum erythropoietin level, makes the diagnosis unlikely. Differential diagnosis in ET includes reactive thrombocytosis, chronic myeloid leukemia, and prefibrotic myelofibrosis. Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) mutations occur in approximately 55%, 25%, and 3% of ET patients, respectively. The same molecular markers are also present in prefibrotic myelofibrosis, which needs to be morphologically distinguished from ET. Survival and leukemic/fibrotic transformation: Median survivals are ∼14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Life‐expectancy in ET is inferior to the control population. JAK2/CALR mutational status does not affect survival in ET. Risk factors for survival in ET and PV include advanced age, leukocytosis, and thrombosis. Leukemic transformation rates at 20 years are estimated at <10% for PV and 5% for ET; fibrotic transformation rates are slightly higher. Thrombosis risk stratification: Current risk stratification in PV and ET is designed to estimate the likelihood of recurrent thrombosis: high‐risk is defined by the presence of age >60 years or presence of thrombosis history; low‐risk is defined by the absence of both of these two risk factors. Recent data consider JAK2V617F and cardiovascular risk factors as additional risk factors. Presence of extreme thrombocytosis might be associated with acquired von Willebrand syndrome (AvWS) and, therefore, risk of bleeding. Risk‐adapted therapy: The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. In low risk patients, this is accomplished by the use of low‐dose aspirin and phlebotomy (hematocrit target <45%) in PV. In high risk (for thrombosis) patients, treatment with hydroxyurea is additionally recommended. Treatment with busulfan or interferon‐α is usually effective in hydroxyurea failures and the additional value of JAK inhibitor therapy in such cases is limited. Screening for AvWS is recommended before administrating aspirin, in the presence of extreme thrombocytosis. Am. J. Hematol. 90:163–173, 2015. © 2014 Wiley Periodicals, Inc.

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Section: Annual Clinical Updates In Hematological Malignanciesmentioning

confidence: 66%

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

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“…25 Busulfan Favorable outcome has also been reported in single arm studies using oral busulfan. 77 The safety and efficacy of busulfan treatment in ET was recently underlined by a long-term study of 36 patients above age 60 years of age; 78 The issue of drug leukemogenicity 75 Only 2 patients (3.5%) treated with busulfan alone developed acute leukemia.…”

Section: Hydroxyureamentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk‐stratification and management

2018

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Disease Overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive JAK2, CALR, or myeloproliferative leukemia mutations. In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Survival: Median survivals are 14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life‐expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET. Risk of thrombosis is higher in JAK2‐mutated ET. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. Thrombosis Risk: In PV, 2 risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors); in ET, 4 risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wild‐type), low (same as very low but JAK2 mutation present), intermediate (age > 60 years, no thrombosis history, JAK2 wild‐type) and high (thrombosis history present or age > 60 years with JAK2 mutation). Risk‐Adapted Therapy: The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once‐ or twice‐daily aspirin (81 mg), in the absence of contraindications. Very low‐risk ET might not require therapy while aspirin therapy is advised for low‐risk disease. Cytoreductive therapy is recommended for high‐risk ET and PV but it is not mandatory for intermediate‐risk ET. First‐line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second‐line drugs of choice are interferon‐α and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs.

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“…Earlier studies had established radiophosphorus and chlorambucil as being leukemogenic. In hydroxyurea refractory or intolerant cases, second-line therapy with either interferon alpha or busulfan is currently acceptable [45,[78][79][80][81]. To date, there is no convincing evidence to implicate either hydroxyurea or busulfan as being leukemogenic in the treatment of either PV or ET [54,82].…”

Section: Essential Thrombocythemia and Polycythemia Veramentioning

confidence: 99%

Myeloproliferative neoplasms 2012: The John M. Bennett 80th birthday anniversary lecture

Tefferi

2012

Leukemia Research

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Busulphan is safe and efficient treatment in elderly patients with essential thrombocythemia

Cited by 47 publications

References 6 publications

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk‐stratification and management

Myeloproliferative neoplasms 2012: The John M. Bennett 80th birthday anniversary lecture

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