Acute myeloid leukemia in patients previously diagnosed with breast cancer: Experience of the GIMEMA group

Objective: To evaluate in a multicenter retrospective study, the clinical and laboratory characteristics and the outcome of patients with acute myeloid leukemia (sAML) previously diagnosed with breast cancer (BC) among an adult acute leukemia population. Patients and methods: Between June 1992 and July 1996, 3934 new cases of adults with acute leukemia were recorded in GIMEMA Archive of Adult Acute Leukemia (2964 AML, 901 ALL, 69 acute leukemia expressing both myeloid and lymphoid surface markers). Results: Two hundred patients (5.1%) presented with a history of previous malignancy (21 of them were affected by ALL and 179 by AML). Among sAML, 37 patients (29%) had a previous breast cancer. They consisted of 36 females and 1 male, median age 56 years, range 34-87. The median latency between the 2 malignancies was 54 months (range 5-379). Twenty-seven patients received chemo- and/or radiotherapy for breast cancer (7 only chemotherapy, 6 only radiotherapy, and 14 combined treatment). All patients were surgically treated but in 10 patients surgical debridement was the sole therapy for breast cancer. The drugs most frequently employed were alkylating agents (18 patients), topoisomerase II inhibitors (9 patients), antimetabolites (20 patients) (CMF, CEF and MMM combinations). At onset of sAML the median WBC count was 7.7 × 109/1 (0.8-153) and the median platelet count was 33.5 × 109/1 (3-305). Considering morphological features, FAB subtypes were 4 M0, 5 M1, 11 M2, 5 M3, 8 M4, 3 M5, and 1 M6. Cytogenetic study was performed on 28 patients and 12 of them presented abnormalities. It is noteworthy that chromosome 5 or 7 abnormalities (typically observed in those patients treated with alkylating agents) were present only in three cases. Thirty-four patients received chemotherapy for sAML, and twenty-five of them achieved a CR (74%), with a median duration of twenty-eight weeks (5-280+). The overall survival was 8 months (1-80+). Discussion: The high number of sAML we observed in patients with a previous breast cancer, may be due to the fact that this malignancy is the most frequent neoplasm in women and by the high probability of cure with a consequent long disease-free survival. Our results suggest that the risk of sAML after recovery from breast cancer is increasing due to the rise in the number of patients cured from breast cancer, and in the future could be a relevant problem for haematologists

The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (≥500/µL) and platelets (≥20,000/µL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT

Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura : A Single Technology Appraisal

Evidence Review Group (ERG) final report for the National Institute for Health and Clinical ExcellencePublisher PD

Autologous Stem Cell Transplantation In Multiple Myeloma

Background. Multiple myeloma (MM) is the second most common hematologic malignancy after lymphomas In Finland: the annual incidence of MM is approximately 200. For three decades the median survival remained at 3 to 4 years from diagnosis until high-dose melphalan treatment supported by autologous stem cell transplantation (ASCT) became the standard of care for newly diagnosed MM since the mid 1990’s and the median survival increased to 5 – 6 years. This study focuses on three important aspects of ASCT, namely 1) stem cell mobilization, 2) single vs. double ASCT as initial treatment, and 3) the role of minimal residual disease (MRD) for longterm outcome. Aim. The aim of this series of studies was to evaluate the outcomes of MM patients and the ASCT procedure at the Turku University Central Hospital, Finland. First, we tried to identify which factors predict unsuccessful mobilization of autologous stem cells. Second, we compared the use of short-acting granulocyte-colony stimulating factor (GCSF) with long-acting G-CSF as mobilization agents. Third, one and two successive ASCTs were compared in 100 patients with MM. Fourth, for patients in complete response (CR) after stem cell transplantation (SCT), patient-specific probes for quantitative allele-specific oligonucleotide polymerase-chain reaction (qASO-PCR) measurements were designed to evaluate MRD and its importance for long-term outcome. Results. The quantity of previous chemotherapy and previous interferon use were significant pre-mobilization factors that predicted mobilization failure, together with some factors related to mobilization therapy itself, such as duration and degree of cytopenias and occurrence of sepsis. Short-acting and long-acting G-CSF combined with chemotherapy were comparable as stem cells mobilizers. The progression free (PFS) and overall survival (OS) tended to be longer after double ASCT than after single ASCT with a median follow-up time of 4 years, but this difference disappeared as the follow-up time increased. qASO-PCR was a good and sensitive divider of the CR patients into two prognostic groups: MRD low/negative (≤ 0.01%) and MRD high (>0.01%) groups with a significant difference in PFS and suggestively also in OS. Conclusions. When the factors prediciting a poor outcome of stem cell mobilization prevail, it is possible to identify those patients who need specific efforts to maximize the mobilization efficacy. Long-acting pegfilgrastim is a practical and effective alternative to short-acting filgrastim for mobilization therapy. There is no need to perform double ASCT on all eligible patients. MRD assessment with qASO-PCR is a sensitive method for evaluation of the depth of the CR response and can be used to predict long-term outcome after ACST.Siirretty Doriast

Die Auswirkung der Melphalan-Dosierung zur Konditionierung vor autologer Stammzelltherapie bei PatientInnen mit einem Multiplen Myelom: eine retrospektive Kohortenanalyse

Die autologe Stammzelltherapie (ASZT) nach Konditionierung mit Melphalan 200mg/m² (Mel200) ist die Standardtherapie bei PatientInnen mit einem Multiplen Myelom (MM). Dosisreduktion von Melphalan (MelRed) kommt zum Einsatz, wenn es Bedenken gibt, dass die Toxizität eine verstärkte Rolle spielt. Ob eine MelRed gleiche Ergebnisse wie Mel200 erzielen kann ist unsicher und wird kontrovers diskutiert. Ziel dieser Promotionsarbeit war es, die Sicherheit und Effektivität unterschiedlicher Melphalan-Dosierungen zu vergleichen. Hierfür wurden PatientInnen mit MM, die am Universitätsklinikum Jena zwischen 2003 und 2017 stammzelltransplantiert wurden, retrospektiv analysiert. Insbesondere wurde das progressionsfreie Überleben (PFS) und das gesamte Überleben (OS), als auch das Auftreten von Toxizität und Rezidiven verglichen. In dieser Arbeit wurden die Daten von 655 PatientInnen, die aufgrund eines MM im Zeitraum von 2003 bis 2017 im Universitätsklinikum Jena behandelt wurden, untersucht. In unserer Studie konnten wir zeigen, dass Mel200 in Bezug auf PFS und OS einem Konditionierungsregime mit MelRed überlegen ist. Mel200 besaß ein signifikant längeres PFS als MelRed. Hierbei konnten wir keine signifikanten Unterschiede hinsichtlich Nebenwirkungen beobachten. Wir konnten außerdem zeigen, dass ein möglichst tiefes Ansprechen auf die Therapie nach ASZT mit einem verlängerten PFS einhergeht. PatientInnen, die mit Mel200 konditioniert wurden, erreichten signifikant häufiger mindestens eine „very good partial response“ nach ASZT. Mel200 stellt ein sicheres und effektives Konditionierungsregime vor ASZT bei PatientInnen mit MM dar und sollte weiterhin als Standardregime gesehen werden. Die Ergebnisse dieser Promotionsarbeit wurden in dem Bone Marrow Transplantation Journal im Dezember 2020 veröffentlicht mit dem Titel „Melphalan 200 mg/m2 does not increase toxicity and improves survival in comparison to reduced doses of melphalan in multiple myeloma patients"

Factors affecting adherence to guidelines for antithrombotic therapy in elderly patients with atrial fibrillation admitted to internal medicine wards

Current guidelines for ischemic stroke prevention in atrial fibrillation or flutter (AFF) recommend Vitamin K antagonists (VKAs) for patients at high-intermediate risk and aspirin for those at intermediate-low risk. The cost-effectiveness of these treatments was demonstrated also in elderly patients. However, there are several reports that emphasize the underuse of pharmacological prophylaxis of cardio-embolism in patients with AFF in different health care settings. AIMS: To evaluate the adherence to current guidelines on cardio-embolic prophylaxis in elderly (> 65 years old) patients admitted with an established diagnosis of AFF to the Italian internal medicine wards participating in REPOSI registry, a project on polypathologies/polytherapies stemming from the collaboration between the Italian Society of Internal Medicine and the Mario Negri Institute of Pharmacological Research; to investigate whether or not hospitalization had an impact on guidelines adherence; to test the role of possible modifiers of VKAs prescription. METHODS: We retrospectively analyzed registry data collected from January to December 2008 and assessed the prevalence of patients with AFF at admission and the prevalence of risk factors for cardio-embolism. After stratifying the patients according to their CHADS(2) score the percentage of appropriateness of antithrombotic therapy prescription was evaluated both at admission and at discharge. Univariable and multivariable logistic regression models were employed to verify whether or not socio-demographic (age >80years, living alone) and clinical features (previous or recent bleeding, cranio-facial trauma, cancer, dementia) modified the frequency and modalities of antithrombotic drugs prescription at admission and discharge. RESULTS: Among the 1332 REPOSI patients, 247 were admitted with AFF. At admission, CHADS(2) score was ≥ 2 in 68.4% of patients, at discharge in 75.9%. Among patients with AFF 26.5% at admission and 32.8% at discharge were not on any antithrombotic therapy, and 43.7% at admission and 40.9% at discharge were not taking an appropriate therapy according to the CHADS(2) score. The higher the level of cardio-embolic risk the higher was the percentage of antiplatelet- but not of VKAs-treated patients. At admission or at discharge, both at univariable and at multivariable logistic regression, only an age >80 years and a diagnosis of cancer, previous or active, had a statistically significant negative effect on VKAs prescription. Moreover, only a positive history of bleeding events (past or present) was independently associated to no VKA prescription at discharge in patients who were on VKA therapy at admission. If heparin was considered as an appropriate therapy for patients with indication for VKAs, the percentage of patients admitted or discharged on appropriate therapy became respectively 43.7% and 53.4%. CONCLUSION: Among elderly patients admitted with a diagnosis of AFF to internal medicine wards, an appropriate antithrombotic prophylaxis was taken by less than 50%, with an underuse of VKAs prescription independently of the level of cardio-embolic risk. Hospitalization did not improve the adherence to guideline

Sex-Differences in the Pattern of Comorbidities, Functional Independence, and Mortality in Elderly Inpatients: Evidence from the RePoSI Register.

BACKGROUND: The RePoSi study has provided data on comorbidities, polypharmacy, and sex dimorphism in hospitalised elderly patients. METHODS: We retrospectively analysed data collected from the 2010, 2012, 2014, and 2016 data sets of the RePoSi register. The aim of this study was to explore the sex-differences and to validate the multivariate model in the entire dataset with an expanded follow-up at 1 year. RESULTS: Among 4714 patients, 51% were women and 49% were men. The disease distribution showed that diabetes, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy were more frequent in men but that hypertension, anaemia, osteoarthritis, depression, and diverticulitis disease were more common in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment, mood disorders, and disability in daily life measured by the Barthel Index (BI) were worse in women. In the multivariate analysis, BI, CIRS, and malignancy significantly increased the risk of death in men at the 1-year follow-up, while age was independently associated with mortality in women. CONCLUSIONS: Our study highlighted the relevance and the validity of our previous predictive model in the identification of sex dimorphism in hospitalised elderly patients underscoring the need of sex-personalised health-care

Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards.

BACKGROUND: Chronic pain is a frequent characteristic of elderly people and represents an actual and still poorly debated topic. OBJECTIVE: We investigated pain prevalence and intensity, and its pharmacological therapy in elderly patients hospitalized in 101 internal medicine wards. METHODS: Taking advantage of the "REgistro POliterapie Società Italiana Medicina Interna" (REPOSI), we collected 2535 patients of whom almost a quarter was older than 85 years old. Among them, 582 patients were affected by pain (either chronic or acute) and 296 were diagnosed with chronic pain. RESULTS: Patients with pain showed worse cognitive status, higher depression and comorbidities, and a longer duration of hospital stay compared to those without pain (all p < .0366). Patients with chronic pain revealed lower level of independency in their daily life, worse cognitive status and higher level of depression compared to acute pain patients (all p < .0156). Moreover, most of them were not treated for pain at admission (73.4%) and half of them was not treated with any analgesic drug at discharge (50.5%). This difference affected also the reported levels of pain intensity. Patients who received analgesics at both admission and discharge remained stable (p = .172). Conversely, those not treated at admission who received an analgesic treatment during the hospital stay decreased their perceived pain (p < .0001). CONCLUSIONS: Our results show the need to focus more attention on the pharmacological treatment of chronic pain, especially in hospitalized elderly patients, in order to support them and facilitate their daily life after hospital discharge

Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies

A reduced-intensity conditioning regimen was investigated in 45 patients with hematologic malignancies who were considered poor candidates for conventional myeloablative regimens. Median patient age was 49 years. Twenty-six patients previously failed autologous transplantation, and 18 patients had a refractory disease at the time of transplantation. In order to decrease nonrelapse mortality, and enhance the graft-versus-tumor effect, a program was designed in which a reduced conditioning with thiotepa, fludarabine, and cyclophosphamide was associated with programmed reinfusions of donor lymphocytes for patients without graft-versus-host disease (GVHD), not achieving clinical and molecular remission after transplantation. GVHD prophylaxis consisted of cyclosporine A and methotrexate. Seventeen patients received marrow cells and 28 received mobilized hematopoietic cells. All patients engrafted. The probability of grades II-IV and III-IV acute GVHD were 47% and 13%, respectively. The probability of nonrelapse mortality, progression-free survival, and overall survival were 13%, 57%, and 53%, respectively. Thirteen patients in complete remission had a polymerase chain reaction marker for minimal disease monitoring; 10 achieved molecular remission after transplantation. Nine patients received donor lymphocytes: one patient with mantle cell lymphoma had a minimal response, one patient with refractory anemia with excess of blasts in transformation achieved complete remission, and 7 patients did not respond. At a median follow-up of 385 days (range, 24 to 820 days), 25 patients (55%) were alive in complete remission. Although longer follow-up is needed to evaluate the long-term outcome, the study shows that this regimen is associated with a durable engraftment, has a low nonrelapse mortality rate, and can induce clinical and molecular remissions