Acute myeloid leukemia (AML) with hyperleukocytosis is associated to high early mortality rates and needs aggressive treatment. Induction chemotherapy (ICH), leukapheresis and hydroxyurea (HU) are the most frequent used leukoreductive strategies. Delay in ICH is very common, leukapheresis is not widely available and hydroxyurea and leukapheresis do not modify early mortality rates. Therefore alternative strategies to leukoreduce patients with AML and hyperleukocytosis are needed. Vinblastine is widely available, cheap, with preclinical activity and promising results in relapsed AML. We explored the leukoreductive power of a single dose of vinblastine in patients with newly diagnosed AML and hyperleukocytosis.
Patients and methods
We conducted a prospective pilot study that included consecutive patients with newly diagnosed non-M3 AML, aged 16 to 60 years, and with a WBC ≥50,000/µL at time of presentation and in whom immediate ICH with 7+3 was not possible because of hospital limitations (i.e. delay in ICH drug availability). We excluded patients with PML/RAR-alfa rearrangement and/or t(15;17), poor performance status (ECOG >2), any preceding chemotherapy, organic dysfunction (defined as a modified Marshall score ≥2) or pregnancy. After diagnostic confirmation, a single dose of vinblastine at 6 mg/m2 i.v. was administered. We documented leukocytes (WBC) and number of blasts on the day of vinblastine administration (0h) and 48 hours later. We represented the achieved leukoreduction with boxplots and compared the absolute reduction in WBC (delta WBC) and blasts (delta blasts) after vinblastine administration. We compared the leukoreductive power of vinblastine to other leukoreductive strategies (HU, leukapheresis). We calculated toxicities (grade 4 neutropenia and thrombocytopenia), median length of hospitalization and parental antibiotics, and overall survival (OS). We documented cases of disseminated intravascular coagulation, leukostasis and tumor lysis syndrome. This study complies with the Declaration of Helsinki, and our local ethics committee. Results
A total of 11 patients were enrolled in the study, seven were men (63.6%), with a median age of 48 (21-78) years. Median follow-up was 21 days (2-833 days). The most frequent morphologic subtype was M4 (3, 27.3%), M5 (2, 18.2%) and M2 (2, 18.2%). Cytogenetics were obtained in three cases (27.3%) and all of them were classified as intermediate risk. Forty eight hours after vinblastine administration the WBC lowered from 122x109/L (50.1-380) to 47.3x109/L (22.1-170) representing a 54% (26.7-84.2) decrese (p=0.0001) (figure 1) while blasts number lowered from 204 x 109/L (47.8-361) to 6.4 x 109/L (0-1.6) representing a 85.7% (75-100) decrease (p=0.005) (figure 1). In Table 1 we compare our results with other strategies. All patients experienced grade 4 neutropenia and thrombocytopenia. There were no cases of disseminated intravascular coagulation, leukostasis or tumor lysis syndrome. Severe infections (grade III-IV) occurred in 8 patients (two patients presented neutropenic colitis, five with severe pneumonia, and one SARS-COV2). Four patients presented septic shock and died during induction therapy. Median length of hospitalization and parental antibiotics were 19 days (2-30) and 7 days (range, 2-24), respectively. A CR was achieved in 4 patients (36.4%) after one induction cycle. One patient presented refractory disease and five died before response evaluation. One patient relapsed at 16 months of follow-up. Median OS was 11 months (0-31.8). Allogeneic stem cell transplantation was performed in 1 patient.
We documented a marked reduction in both WBC and blasts after 48 hours of vinblastine administration. Our study suggests that the leukoreductive power of a single dose of vinblastine is similar to HU and leukapheresis in patients with AML with hyperleukocytosis. Vinblastine is a widely available, cheap and myelotoxic drug that could extend the arsenal to treat newly diagnosed AML with hyperleukocytosis.
Gomez-Almaguer:AstraZeneca:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Pfizer:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene/BMS:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Amgen:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AbbVie:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
Asterisk with author names denotes non-ASH members.