Feasibility and Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in 30 Patients with Poor Risk Acute Myeloid Leukemia Older than 60 Years

We report on the feasibility and outcome of allogeneic SCT (allo-SCT) in 30 poor risk AML patients older than 60 years. Median age at transplant was 63 years (range 60-70 years) and 18/30 (60%) cases were in complete remission. Donors were MUD in 40% and sibling in 60% of cases. Twenty-six of 30 patients (87%) received a reduced intensity conditioning regimen (RIC). The hematopoietic cell transplantation specific comorbidity index (HCT-CI) was two or less in 12/30 cases and three or more in 18/30 cases. All patients engrafted. One year Nonrelapse mortality (NRM) rate was 20% (6/30 cases). After a median follow-up of 16 months 17/30 patients (57%) were alive and in complete remission while 13/30 (43%) have died (leukemia refractory or relapse 7/13 and NRM 6/13). Median Overall Survival for the whole patient population was 28 months. The Overall Survival did not differ between unrelated and related donors. The patients transplanted in complete remission had a significantly lower survival rate and relapse rate compared to those transplanted with refractory or relapsed AML (P= 0.0004 and P= 0.008 respectively). The patients with a low HCT-CI (2 or less) had a significantly lower NRM (P = 0.03) and survival rate (P = 0.02) compared to those with HCT-CI 3 or more. Taking into account that this is a retrospective analysis with a small number of cases, these results confirm the feasibility of allo-SCT for high risk AML patients older than 60 years. Outcome was significantly influenced by status of disease at transplant and by HCT-CI. We also confirm that for older patients lacking a family donor MUD can provide a suitable alternative option

SOGS-RA gambling scores and substance use in adolescents

Background and aims There is a well-established association between pathological gambling and substance use disorders in adolescents. The aim of this study was to shed light on the association between adolescents’ different levels of involvement in gambling activities and substance use (smoking tobacco and cannabis and drinking alcoholic beverages), based on a large sample. Methods A survey was conducted in 2013 on 34,746 students attending 619 secondary schools, who formed a representative sample of the Italian 15- to 19-year-old population. The prevalence of different categories of gamblers was estimated by age group and gender. A multiple correspondence analysis (CA) was conducted to explain the multivariate associations between substance use and gambling. Results The prevalence of problem gambling was 2.7% among the 15- to 17-year-olds, and rose to 3.6% among the 18- and 19-year-olds. Multiple CA revealed that, even when it does not reach risk-related or problem levels, gambling is associated with the use of alcohol and tobacco. In particular, the analysis showed that non-problem gambling levels were associated with alcohol and tobacco use at least once in the previous month, and that higher-risk gambling levels related to the use of cannabis and episodes of drunkenness at least once in the previous month. Conclusion This study found that any gambling behavior, even below risk-related or problem levels, was associated with some degree of substance use by youths, and that adolescents’ levels of gambling lay along a continuum of the categories of substance use

Bortezomib Plus Dexamethasone Followed by Escalating Donor Lymphocyte Infusions for Patients with Multiple Myeloma Relapsing or Progressing after Allogeneic Stem Cell Transplantation

Abstract Multiple myeloma relapsing after allogeneic stem cell transplantation (alloSCT) has a poor outcome. To assess the safety and efficacy of bortezomib and dexamethasone (VD) combination followed by donor lymphocyte infusions (DLIs) in myeloma patients relapsing or progressing after alloSCT, a prospective phase II study was designed. The treatment plan consisted of three VD courses followed by escalated doses of DLIs in case of response or at least stable disease. Nineteen patients were enrolled with a median age of 57 years (range, 33 to 67); 14 patients were allografted from human leukocyte antigen–identical siblings and 5 from alternative donors. Sixteen of 19 patients received the planned treatment, but 3 patients did not: 2 patients because of disease progression and 1 refused. After the VD phase the response rate was 62%, with 1 complete remission, 6 very good partial remissions, 5 partial remissions, 2 patients with stable disease, and 5 with progressive disease. After the DLI phase, the response rate was 68%, but a significant upgrade of response was observed: 3 stringent complete remissions, 2 complete remissions, 5 very good partial remissions, 1 partial remission, 4 with stable disease, and 1 with progressive disease. With a median follow-up of 40 months (range, 29 to 68), the 3-year progression-free survival and overall survival rates were 31% and 73%, respectively. Neither unexpected organ toxicities, in particular severe neuropathy, nor severe acute graft-versus-host disease flares were observed. VD-DLIs is a safe treatment for multiple myeloma patients relapsing or progressing after alloSCT and may be effective

Therapeutic Targeting of Acute Myeloid Leukemia by Gemtuzumab Ozogamicin

Simple Summary Gemtuzumab Ozogamicin (GO) is a drug approved for the treatment of acute myeloid leukemia (AML). It targets leukemic cells that express the CD33 molecule on their surface and brings the toxic agent calicheamicin inside the cell to kill it. Several studies have shown that AML patients can benefit of the addition of GO to chemotherapy during induction regimens, pre- and post-transplantation. Moreover, some disease features have been addressed or are under investigation for their capacity to predict response to GO, with the future aim of selecting AML patients that can mostly benefit of GO treatment. Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by genetic and clinical heterogeneity and high mortality. Despite the recent introduction of novel pharmaceutical agents in hemato-oncology, few advancements have been made in AML for decades. In the last years, the therapeutic options have rapidly changed, with the approval of innovative compounds that provide new opportunities, together with new challenges for clinicians: among them, on 1 September, 2017 the Food and Drug Administration granted approval for Gemtuzumab Ozogamicin (GO) in combination with daunorubicin and cytarabine for the treatment of adult patients affected by newly diagnosed CD33(+) AML. Benefits of GO-based regimens were also reported in the pre- and post-transplantation settings. Moreover, several biomarkers of GO response have been suggested, including expression of CD33 and multidrug resistance genes, cytogenetic and molecular profiles, minimal residual disease and stemness signatures. Among them, elevated CD33 expression on blast cells and non-adverse cytogenetic or molecular risk represent largely validated predictors of good response

The role of positron emission tomography with 18F-fluorodeoxyglucose integrated with computed tomography in the evaluation of patients with multiple myeloma undergoing allogeneic stem cell transplantation

Positron emission tomography (PET) integrated with computed tomography (PET/CT) has been reported to be useful for screening myelomatous lesions at diagnosis in patients with multiple myeloma (MM) and for monitoring response to autologous stem cell transplantation (auto-SCT). The aim of the study was to evaluate the prognostic significance of PET/CT in MM patients who received allogeneic stem cell transplantation (allo-SCT). Patients who underwent upfront auto-SCT followed by allo-SCT, either as consolidation or salvage treatment, were studied with PET/CT before and/or within 6 months after allo-SCT. The number, the maximum standard uptake value (SUV), and the location (medullary or extramedullary) of focal lesions (FLs) were recorded and investigated as predictors of progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. Fifty-four patients had a PET/CT scan before allo-SCT. Of these, 22 patients (41%) had a negative PET/CT scan, 11 patients (20%) showed 1 to 3 FLs, and 21 patients (39%) had either a diffuse bone marrow involvement or more than 3 FLs. SUV was >4.2 in 21 patients (39%) and extramedullary disease (EMD) was present in 6 patients (11%). Multivariate analysis of prognostic factors before allo-SCT showed that persistence of EMD at transplantation was an independent predictor of poor PFS, whereas OS was negatively influenced by unrelated donor and SUV > 4.2. Fifty-nine patients had a PET/CT scan within 6 months after allo-SCT. Multivariate analysis of post-treatment variables showed that persistence of EMD and failure to obtain complete response or very good partial response after allo-SCT were strongly associated with shorter PFS and OS. Of the 46 patients with evaluable PET/CT scans both before and 6 months after allo-SCT, the 23 patients who maintained or reached a PET complete remission showed a significantly prolonged PFS and OS compared with the 23 patients with persistence of any PET positivity (2-year PFS: 51% versus 25%, P = .03; 2-year OS: 81% versus 47%, P = .001). This study indicates that PET/CT imaging before and after allo-SCT is significantly associated with the outcome, suggesting the utility of this technique for MM staging before allo-SCT and for response monitoring after the transplantation

Risk Factors and Outcomes of Infections by Multidrug-Resistant Gram-Negative Bacteria in Patients Undergoing Hematopoietic Stem Cell Transplantation

Abstract The objective of this study was to determine risk factors and outcomes of infections by multidrug-resistant gram-negative (MDR GN) bacteria in 241 recipients of hematopoietic stem cell transplantation (HSCT). The cumulative incidence of infections was 10.5% (95% CI, 12.0% to 25.8%), with 57% of infections occurring during the period of severe neutropenia (neutrophil count  6 /L). In multivariate analysis, allogeneic transplant and colonization with MDR GN bacteria at admission to the transplant unit were significantly associated with an increased risk of infection. Although we observed neither transplant-related mortality (TRM) nor deaths due to infections by MDR GN bacteria after autologous transplant, in the allogeneic setting a significant difference was reported in terms of overall survival (OS) and TRM between patients who developed infections and those who did not (1-year OS, 39% versus 68%; 1-year TRM, 42% versus 19%). In multivariate analysis, refractory disease and development of grades III to IV graft-versus-host disease (GVHD) were factors that affected both TRM and OS, whereas occurrence of infections by MDR GN pathogens significantly reduced OS. We conclude that eligibility to allogeneic HSCT in MDR GN bacteria carriers should be carefully evaluated together with all other factors that independently influence outcome (disease status, donor, and GVHD risk)

CPX-351 and allogeneic stem cell transplant for a therapy-related acute myeloid leukemia that developed after treatment of acute promyelocytic leukemia: a case report and review of the literature

Therapy-related myeloid neoplasms (t-MNs), which develop after cytotoxic, radiation, or immunosuppressive therapy for an unrelated disease, account for 7%–8% of acute myeloid leukemia (AML). Worse outcomes and consequently shortened survival are associated with t-MNs as compared with de novo AML. Therapy-related MNs are being reported with increasing frequency in successfully treated acute promyelocytic leukemia (APL), in particular, before the introduction of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO). Considering the high curability of APL, t-MNs represent one of the prognosis-limiting factors in this setting of leukemia. We report our experience with a patient who developed t-AML 15 years after treatment for APL. Treatment included three cycles of chemotherapy with CPX-351 (Vyxeos, Jazz Pharmaceuticals) followed, as in remission, by an allogeneic hematopoietic stem cell transplant. A review of available literature was also included