High-Intensity Induction Chemotherapy Is Feasible for Elderly Patients with Acute Myeloid Leukemia.

BACKGROUND: The prognosis of elderly patients with acute myeloid leukemia (AML) is poor, and the best treatment is controversial. Since the majority of AML patients are older than 60 years, identification of those who might benefit from intensive treatment is essential. METHODS: Data from electronic charts of consecutive AML patients treated in our center were analyzed. Eligibility criteria included newly diagnosed de novo or secondary AML, an age of 60 years or older, and intensive induction treatment. RESULTS: Sixty-two patients were included in the analysis. Forty-six patients (74%) achieved complete remission (CR) after 1-2 intensive induction courses. Twenty of them received consolidation with conventional chemotherapy, 20 proceeded to allogeneic hematopoietic cell transplantation (allo-HCT), and 6 were ineligible for further treatment. The projected overall survival (OS) at 2 and 3 years was 28 and 23%, respectively. A normal karyotype, CR achievement, and allo-HCT were associated with improved OS, while an Eastern Cooperative Oncology Group performance status of 0-1 was borderline associated. The median survival and disease-free survival at 2 years was 18.7 months and 49%, respectively, for patients who underwent allo-HCT in CR1, compared to 12.8 months and 25%, respectively, for those who did not. CONCLUSION: Based on our data, selected eligible elderly AML patients might benefit from intensive treatment.

Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a phase II study. GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low-dose anti-T cell globulin. CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidences of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double-blind controlled study is warranted. (clinicaltrials.gov: NCT01385124).

Tailoring the GVHD prophylaxis regimen according to transplantation associated toxicities-Substituting the 3rd dose of methotrexate to mycophenolate mofetil.

We hypothesized that in patients with early post allogeneic transplantation toxicities, the omission of the 3rd dose of methotrexate with concomitant starting of MMF would favorably affect complications. We found a higher incidence of grade 2-4 acute GVHD in patients given two doses methotrexate and MMF (n=31) compared to those given three courses of methotrexate (n=70) (p=.004), while grade 3-4 was similar. Other transplantation outcomes, including overall regimen-related-toxicity, were comparable. We conclude that tailoring the GVHD prophylaxis regimen may decrease the early post transplantation complications, however this come at the extent of a higher incidence of non-severe acute GVHD.

Subcutaneous versus intravenous granulocyte colony stimulating factor for the treatment of neutropenia in hospitalized hemato-oncological patients: randomized controlled trial.

Intravenous (IV) granulocyte colony stimulating factor (G-CSF) might be safer and more convenient than subcutaneous (SC) administration to hospitalized hemato-oncological patients receiving chemotherapy. To compare IV vs. SC G-CSF administration, we conducted a randomized, open-label trial. We included inpatients receiving chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma or multiple myeloma, and allogeneic or autologous hematopoietic cell transplantation (HCT). Patients were randomized to 5 mcg/kg single daily dose of IV bolus versus SC filgrastim given for its clinical indications. Patients were crossed-over to the alternate study arm on the subsequent chemotherapy course. The primary outcomes were time from initiation of filgrastim to recovery of stable neutrophil count of >500 cells/µL and a composite clinical outcome of infection or death assessed for the first course post-randomization. The study was stopped on the second interim analysis. Of 120 patients randomized, 118 were evaluated in the first treatment course. The mean time to neutropenia resolution was longer with IV G-CSF [7.9 days, 95% confidence interval (CI) 6.6-9.1] compared with SC G-CSF (5.4 days, 95% CI 4.6-6.2), log-rank P = 0.001. Longer neutropenia duration was observed in all patient subgroups, except for patients undergoing autologous HCT. There was no significant difference between groups in the occurrence of infection or death, but more deaths were observed with IV (4/57, 7%) versus SC (1/61, 1.6%) G-CSF administration, P = 0.196. Similar results were observed when all 158 courses following cross-over were analyzed. Patients reported similar pain and satisfaction scores in both groups. Bolus IV administration of G-CSF results in longer neutropenia duration than SC administration, with no difference in clinical or quality-of-life measures.

Toxicity of autologous hematopoietic cell transplantation in patients with multiple myeloma - comparison between two different induction regimens.

BACKGROUND: Induction therapy in patients with multiple myeloma has evolved from chemotherapy-based to novel agents-based regimens. We compared autologous hematopoietic cell transplantation (HCT)-associated toxicity in patients induced with VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatinum, adriamycin, cyclophosphamide, and etoposide) to that of patients induced with novel agents-only therapy. METHODS: We reviewed medical charts of all patients with multiple myeloma who were given induction therapy and HCT. RESULTS: Between the years 2007 and 2011, 38 patients received VTD-PACE, and 31 patients received novel agents-only regimen. Mean time to neutrophil and platelets recovery was longer in patients given VTD-PACE compared with those given novel agents-only regimen (7 vs. 6 d, p = 0.0002 and 11 vs. 10 d, p = 0.04, respectively). We observed higher rates of grade 2-4 mucositis and parenteral narcotic analgesia administration in the patients given VTD-PACE (45% vs. 19%, p = 0.05 and 37% vs. 12%, p = 0.07, respectively). Progression free survival and overall survival were not statistically significantly different between the two groups. CONCLUSIONS: A more intensive induction regimen was associated with slightly delayed counts recovery and a higher rate of mucositis during HCT compared with novel agents-only regimens. A longer follow-up is needed to assess long-term disease control of the two different regimens.

Characteristics of initial compared with subsequent bacterial infections among hospitalised haemato-oncological patients.

Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever.

Surveillance of infectious complications in hemato-oncological patients.

BACKGROUND: Monitoring the rate of infections in individual centers that treat patients with hematological malignancies is of major importance. However, there are no uniform guidelines for infection surveillance. OBJECTIVES: To describe the epidemiology of bacterial and fungal infections in a single hematology ward and to compare methods for reporting surveillance and infection rates in other centers in Israel. METHODS: We conducted a prospective surveillance of all patients admitted to our hematology ward, applying standard definitions for invasive fungal infections and adapting definitions for non-fungal infections. Incidence rates were calculated using patients, admissions, hospital days and neutropenia days. We performed a search for other reported surveillance studies in Israel. , RESULTS: We detected 79 infectious episodes among 159 patients admitted to the hematology ward during 1 year. Using neutropenia days as the denominator for calculation of incidence discriminated best between patients at high and low risk for infection. The incidence of invasive fungal infections was 7, 10 and 18 per 1000 neutropenia days, among all patients, those with acute leukemia and those with acute leukemia undergoing induction therapy, respectively. Only 10 reports from Israel were identified, 6 of which were prospective. Our data could not be compared to these reports because of the varying definitions and denominators used. CONCLUSIONS: Hematology centers should monitor infection rates and report them in a uniform methodology.