title: Busulfan in patients with polycythemia vera or essential thrombocythemia refractory or intolerant to hydroxyurea.
abstract: Therapeutic options for patients with polycythemia vera (PV) and essential thrombocythemia (ET) resistant or intolerant to hydroxyurea are limited. Busulfan is effective as first-line therapy, but there is scarce information on this drug as second-line treatment. The efficacy of busulfan in patients with advanced PV or ET refractory or intolerant to hydroxyurea was assessed in 36 patients (PV n = 15, ET n = 21) treated for a median of 256 days. Complete hematological response (CHR) was achieved in 83 % of patients, after a median time of 203 days (range 92-313). The probability of sustained CHR at 1 and 2 years was 87 and 62 %, respectively. Time to CHR was shorter in patients treated with ≥14 mg of busulfan per week than with lower doses (141 versus 336 days, p = 0.01). Partial molecular response was achieved in three out of nine (33 %) patients. Busulfan was stopped in 27 patients (75 %) due to CHR achievement in 18 cases (67 %), hematological toxicity in 8 cases (30 %), and disease transformation in 1 case. With a median follow-up of 721 days, six patients have died, with the probability of survival at 2 years being 85 %. The probability of thrombosis at 2 years was 11 %. Transformation into acute leukemia or myelodysplastic syndrome was observed in three cases, all of them in a JAK2V617F-negative clone carrying additional mutations. Busulfan, at a dose of 2 mg/day, is an effective option for elderly patients with PV or ET who fail to hydroxyurea, but a significant rate of transformation was observed.
authors: Hematology Department, Universitat Autònoma de Barcelona, Hospital del Mar-IMIM, Passeig Marítim 25-29, 08003, Barcelona, Spain, 95967@parcdesalutmar.cat.
authors: Alberto
authors: A
authors: Alvarez-Larrán
authors: Luz
authors: L
authors: Martínez-Avilés
authors: Juan Carlos
authors: JC
authors: Hernández-Boluda
authors: Francisca
authors: F
authors: Ferrer-Marín
authors: María Luisa
authors: ML
authors: Antelo
authors: Carmen
authors: C
authors: Burgaleta
authors: M Isabel
authors: MI
authors: Mata
authors: Blanca
authors: B
authors: Xicoy
authors: Alejandra
authors: A
authors: Martínez-Trillos
authors: M Teresa
authors: MT
authors: Gómez-Casares
authors: M Antonia
authors: MA
authors: Durán
authors: Bárbara
authors: B
authors: Marcote
authors: Agueda
authors: A
authors: Ancochea
authors: Alicia
authors: A
authors: Senín
authors: Anna
authors: A
authors: Angona
authors: Montse
authors: M
authors: Gómez
authors: Vicente
authors: V
authors: Vicente
authors: Francisco
authors: F
authors: Cervantes
authors: Beatriz
authors: B
authors: Bellosillo
authors: Carles
authors: C
authors: Besses
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000477:Alkylating Agents / Q000627:therapeutic use*; D001772:Blood Cell Count; D002066:Busulfan / Q000627:therapeutic use*; D015897:Comorbidity; D018450:Disease Progression; D004351:Drug Resistance; D057915:Drug Substitution; D005260:Female; D006400:Hematocrit; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D012074:Remission Induction; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D013927:Thrombosis / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000477:Alkylating Agents; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D002066:Busulfan; D006918:Hydroxyurea