Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network.

PURPOSE: Hydroxyurea (HY) is a reference treatment of advanced myeloproliferative neoplasms. We conducted a randomized phase III trial comparing decitabine (DAC) and HY in advanced myeloproliferative chronic myelomonocytic leukemias (CMML). PATIENTS AND METHODS: Newly diagnosed myeloproliferative CMML patients with advanced disease were randomly assigned 1:1 to intravenous DAC (20 mg/m2/d days 1-5) or HY (1-4 g/d) in 28-day cycles. The primary end point was event-free survival (EFS), events being death and acute myelomonocytic leukemia (AML) transformation or progression. RESULTS: One-hundred seventy patients received DAC (n = 84) or HY (n = 86). Median age was 72 and 74 years, and median WBC count 32.5 × 109/L and 31.2 × 109/L in the DAC and HY arms, respectively. Thirty-three percent of DAC and 31% of HY patients had CMML-2. Patients received a median of five DAC and six HY cycles. With a median follow-up of 17.5 months, median EFS was 12.1 months in the DAC arm and 10.3 months in the HY arm (hazard ratio [HR], 0.83; 95% CI, 0.59 to 1.16; P = .27). There was no significant interaction between treatment effect and blast or platelet count, anemia, CMML Prognostic Scoring System, Groupe Francophone des Myelodysplasies, or CMML Prognostic Scoring System-mol risk. Fifty-three (63%) DAC patients achieved a response compared with 30 (35%) HY patients (P = .0004). Median duration of response was similar in both arms (DAC, 16.3 months; HY, 17.4 months; P = .90). Median overall survival was 18.4 months in the DAC arm and 21.9 months in the HY arm (P = .67). Compared with HY, DAC significantly reduced the risk of CMML progression or transformation to acute myelomonocytic leukemia (cause-specific HR, 0.62; 95% CI, 0.41 to 0.94; P = .005) at the expense of death without progression or transformation (cause-specific HR, 1.55; 95% CI, 0.82 to 2.9; P = .04). CONCLUSION: Compared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML (ClinicalTrials.gov identifier: NCT02214407).

Invasive pulmonary aspergillosis in acute leukemia: a still frequent condition with a negative impact on the overall treatment outcome.

We evaluated the impact of invasive pulmonary aspergillosis (IPA) on epidemiology and outcome in acute leukemia (AL), analyzing all acute myeloid (AML) and acute lymphoblastic leukemia (ALL) consecutively admitted to our Institution during a 5-year period of observation. Only AML patients received anti-mold prophylaxis. Among 175 AL patients (136 AML/39 ALL), possible and proven/probable IPA were diagnosed in 28 (16%). Frequency of IPA was similar in AML (16.2%) and in ALL (15.4%). Two-year overall survival (OS) was significantly affected by IPA (no IPA: 69.8% vs IPA: 31.7% p = .002). OS was similar in patients with proven/probable (28.2%) and possible IPA (36.4%) (p = .003 and .065, respectively). When censoring patients at transplant, IPA still affected 2-year survival (49.6% vs 79.2%, p = .02), but only proven/probable IPA was associated with lower survival (34.7%, p = .0003). IPA negatively impacts on long-term survival of leukemia patients; antifungal prophylaxis should be adopted also during induction in ALL and in AML beyond induction therapy.

The influence of disease and comorbidity risk assessments on the survival of MDS and oligoblastic AML patients treated with 5-azacitidine: A retrospective analysis in ten centers of the "Rete Ematologica Lombarda".

5-Azacytidine is an effective therapy in high risk MDS and oligoblastic AML. This "real life" analysis was made on 185 patients treated with 5-azacytidine in 10 centers afferent to REL ("Rete Ematologica Lombarda"), a network in Lombardia region. The aim was to assess the influence of disease and comorbidity risk assessments on the survival. The results confirm the utility of 5-azacitidine in prolonging OS regardless of advanced age and the presence of comorbidities. They also encourage an early treatment since patients with IPSS-R High risk MDS have better outcome with respect to Very High risk ones. According to the IPSS cytogenetic risk, there was no difference in the outcome between Intermediate and High risk patients. Nevertheless, a poorer cytogenetic risk, according to the IPSS-R cytogenetic stratification, negatively influenced the outcome.

A high-dose bortezomib neuropathy with sensory ataxia and myelin involvement.

Bortezomib, a proteasome inhibitor used in the treatment of multiple myeloma, is known to induce an axonal, dose-dependent neuropathy clinically characterized by pain, paresthesias, burning dysesthesias and numbness. In this study, we describe a patient treated with high-dose bortezomib whose main clinical feature was severe sensory ataxia. Electrodiagnostic studies showed, other than axonal changes, myelin involvement.

Immune-mediated hepatitis-associated aplastic anemia caused by the emergence of a mutant hepatitis B virus undetectable by standard assays.

Hepatitis-associated aplastic anemia (HAA) is characterized by marrow failure developing after acute seronegative hepatitis. A patient with agammaglobulinemia developed HAA in association with HBsAg-negative, hepatitis B virus (HBV) DNA-positive acute hepatitis. Sequence analysis showed several substitutions in the major antigenic determinant of HBsAg, potentially affecting the detection by diagnostic immunoassays. Viral mutants may therefore be implicated as etiologic agents of HBsAg-negative HAA. HBV DNA determination may be necessary to exclude mutant HBV as a cause of HAA, particularly in categories at high risk of mutant selection such as agammaglobulinemic and transplanted patients.

Recombinant granulocyte-colony stimulating factor as treatment for poor prognosis oligoblastic acute myeloid leukemia in elderly patients.

Twenty-five elderly patients with oligoblastic acute myeloid leukemia (AML) received subcutaneous granulocyte colony-stimulating factor (filgrastim) in addition to supportive care. Ninety-two percent of the patients had multilineage dysplasia, 17% hypoplasia, and 48% a high-risk karyotype. During filgrastim treatment neutrophil and platelet counts increased significantly (p<0.0001 and (p=0.042), respectively) and 3/13 patients (23%) no longer required transfusions. A complete peripheral hematologic response (CHR) was obtained in eight (32%) and marrow blast cell clearance (<5%) in five patients (20%), lasting 12 and 10 months, respectively. Filgrastim caused osteomyalgia and fever in 20% of cases. The median survival was 8 months overall, and 15 months in patients who achieved a CHR. Filgrastim may be a useful adjunct to supportive care in elderly patients with poor-risk AML.

Frequency of hepatitis B virus mutant in asymptomatic hepatitis B virus carriers receiving prophylactic lamivudine during chemotherapy for hematologic malignancies.

Hepatitis B virus (HBV) reactivation is a potentially fatal complication of chemotherapy in asymptomatic HBV carriers. Prophylactic lamivudine has proven effective for its prevention, but the potential emergence of lamivudine-resistant HBV YMMD mutants, as shown in patients treated for chronic hepatitis, may limit its use. To evaluate the frequency of HBV YMMD mutant and its clinical significance, we have analysed 32 courses of primary lamivudine prophylaxis given to HBV carriers with haematologic malignancies, from the start until 1-5 months after the end of chemotherapy. Lamivudine was used for a median of 6 months (range 2-24+) and median follow-up was 19.5 months (range 5-40). Four episodes of HBV reactivation with mild hepatitis and no evidence of mutant strain occurred after chemotherapy completion and after lamivudine withdrawal. At follow-up YMMD mutant was detected in one patient with normal transaminase levels, who had been on continuous lamivudine for 20 months. In conclusion, among HBV carriers treated with chemotherapy for haematologic malignancies, the emergence of HBV YMMD mutant occurred in 3.1% of prophylactic lamivudine courses and was of little clinical relevance.