The Real-World Evidence on the Fragility and Its Impact on the Choice of Treatment Regimen in Newly Diagnosed Patients with Multiple Myeloma over 75 Years of Age.

Fragility scales are intended to help in therapeutic decisions. Here, we asked if the fragility assessment in MM patients ≥ 75 years old qualified for treatment by the local physician correlates with the choice of treatment: a two- or three-drug regimens. Between 7/2018 and 12/2019, we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in completely dependent. Patients with more than three comorbidities made up 26.9% (53 patients). Thus, according to the Palumbo calculator, 43 patients were in the intermediate fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received three-drug regimens and 20.3% (40) received two-drug regimens. In each ECOG group, more than three out of four patients received three-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received three-drug regimens. Out of 53 patients with at least four comorbidities, 71.7% received three-drug regimens, and the rest received two-drug regimens. Thirty-four patients from the intermediate fit group (79.0%), and 123 (79.9%) from the frail group received three-drug regimens. Early mortality occurred in 25 patients (12.7%). No one discontinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with triple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations, which brings into question the clinical utility of current fragility scales in everyday practice.

Outcome of a Real-Life Population of Patients With Acute Promyelocytic Leukemia Treated According to the PETHEMA Guidelines: The Polish Adult Leukemia Group (PALG) Experience.

BACKGROUND: Acute promyelocytic leukemia (APL) has a favorable prognosis. However, results of randomized studies do not necessarily reflect the outcomes of a real-life population. PATIENTS AND METHODS: We analyzed 283 unselected APL patients treated in 20 Polish hospitals between 2005 and 2017. All patients were intended to be treated with PETHEMA (Programa Español para el Tratamiento de las Hemopatías Malignas) protocols based on all-trans retinoic acid plus chemotherapy. RESULTS: The probability of overall survival at 4 years was 67%, while event-free survival was 64%. The early death (ED) rate was 20.1% (n = 57), while 3.5% (n = 10) patients died before induction therapy was started. The main causes of ED included hemorrhage (45.6%), infections (17.5%), and differentiation syndrome (14.5%). Of 273 treated patients, 214 (78.4%) experienced hematologic morphologic remission, 2 (0.7%) were found to have resistant disease, 47 (17.2%) could not be evaluated for response because of ED, and in 6 (3.7%) no data concerning the response were available. Multivariate analyses showed that predictors of ED and overall survival were Eastern Cooperative Oncology Group performance status > 2, age > 60 years, and all types of bleeding episodes that occurred before starting therapy, while an additional predictor of event-free survival was high white blood cell count (> 10 109/L). CONCLUSION: ED remains a major problem in APL patients, especially in a real-life population. Shortening of the time between the initial contact with a health care professional, and all-trans retinoic acid administration and the use of appropriate supportive care could improve the outcome of unselected APL population, mainly by reducing the ED rate.

Mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson's disease.

A case is presented of mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson's disease. A 58-year-old female was admitted to the Department of Haematology with deterioration of her general condition, loss of appetite, tiredness and difficulty with mental contact for a few days. Blood and urine cultures for bacteria and fungus, galactomannan antigen were negative. Whole body computed tomography demonstrated bilateral hilar lymphadenopathy with necrotic lesions: splenomegaly with a hypodensive lesion 13 × 20 × 19 mm and lower pulmonary infiltrates suggested fungal etiology. Magnetic resonance imaging of the brain showed thickened meninges. Finally, mucormycosis was diagnosed. Treatment with amphotericin B lipid complex was started, resulting in an partial improvement of the general condition and decreased level of inflammatory markers. However, the patient's condition continued to deteriorate, with sepsis etiology Escherichia coli, and despite the intensive managements she eventually died.

Predictive Model for Infection Risk in Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia Patients Treated With Azacitidine; Azacitidine Infection Risk Model: The Polish Adult Leukemia Group Study.

BACKGROUND: Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) patients, including those treated with azacitidine, are at increased risk for serious infections. The aim of our study was to identify patients with higher infectious risk at the beginning of azacitidine treatment. PATIENTS AND METHODS: We performed a retrospective evaluation of 298 MDS/CMML/AML patients and included in the analysis 232 patients who completed the first 3 cycles of azacitidine therapy or developed Grade III/IV infection before completing the third cycle. RESULTS: Overall, 143 patients (62%) experienced serious infection, and in 94 patients (41%) infection occurred within the first 3 cycles. The following variables were found to have the most significant effect on the infectious risk in multivariate analysis: red blood cell transfusion dependency (odds ratio [OR], 2.38; 97.5% confidence interval [CI], 1.21-4.79), neutropenia <0.8 × 109/L (OR, 3.03; 97.5% CI, 1.66-5.55), platelet count <50 × 109/L (OR, 2.63; 97.5% CI, 1.42-4.76), albumin level <35 g/dL (OR, 2.04; 97.5% CI, 1.01-4.16), and Eastern Cooperative Oncology Group performance status ≥2 (OR, 2.19; 97.5% CI, 1.40-3.54). Each of these variables is assigned 1 point, and the combined score represents the proposed Azacitidine Infection Risk Model. The infection rate in the first 3 cycles of therapy in lower-risk (0-2 score) and higher-risk (3-5 score) patients was 25% and 73%, respectively. The overall survival was significantly reduced in higher-risk patients compared with the lower-risk cohort (8 vs. 29 months). CONCLUSION: We selected a subset with high early risk for serious infection and worse clinical outcome among patients treated with azacitidine.

The efficacy and safety of pomalidomide in relapsed/refractory multiple myeloma in a "real-world" study: Polish Myeloma Group experience.

BACKGROUND: Patients with relapsed/refractory multiple myeloma (RRMM) have poor prognosis. Pomalidomide is an immunomodulatory compound that has demonstrated activity in MM patients with disease refractory to lenalidomide and bortezomib. OBJECTIVES: Participants of clinical trials are highly selected populations; therefore, the aim of this study was to present observations from real practice that might provide important information for practitioners. PATIENTS AND METHODS: We analyzed retrospectively 50 patients treated with pomalidomide in 12 Polish sites between 2014 and 2017. Median age was 63 years, median time since diagnosis 4.5 years and median number of prior regimens 4. RESULTS: The overall response rate was 39.1%. Median progression-free survival (PFS) and overall survival (OS) were 10.0 and 14.0 months, respectively. Previous treatment with immunomodulatory drugs, bortezomib or stem cell transplant had no impact on PFS and OS. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia 24.0%, thrombocytopenia 10.0%, anemia 8.0%). Most common grade 3/4 non-hematologic toxicities were respiratory tract infection (14.0%) and neuropathy (4.0%). CONCLUSIONS: This real-world data have confirmed that pomalidomide is an active drug in RRMM and support results of published clinical trials and other real-world studies.

Prognostic indicators in primary plasma cell leukaemia: a multicentre retrospective study of 117 patients.

We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety-eight patients were treated with novel agents, with an overall response rate of 78%. Fifty-five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median follow-up time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6·3; 35·8) in patients who did not receive ASCT (P = 0·001). Multivariate analyses identified age ≥60 years, platelet count ≤100 × 109 /l and peripheral blood plasma cell count ≥20 × 109 /l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2-3 of these risk factors was 46, 27 and 12 months, respectively (P < 0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated.

Characteristics and outcomes of patients with multiple myeloma aged 21-40 years versus 41-60 years: a multi-institutional case-control study.

We compared the outcomes of multiple myeloma (MM) patients aged 21-40 and 41-60 years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high-risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0·001). Five- and 10-year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0·001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0·001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21-40 years, treated in the era of novel agents have a better OS than their counterparts aged 41-60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM.

Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice.

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575-580, 2016. © 2016 Wiley Periodicals, Inc.

Demographic, Hematologic, and Clinical Features of Myelodysplastic Syndrome Patients: Results from the First Polish Myelodysplastic Syndrome Registry.

Epidemiological studies on myelodysplastic syndromes (MDS) in Middle-Eastern Europe are scarce. No data about the demographic, clinical, and laboratory features of Polish MDS patients have been published. The aim of this study was to assess the epidemiological data and toxic exposure of Polish MDS patients and their association with hematological parameters and clinical outcomes. For 15 months, 966 living MDS patients were enrolled at 24 centers (12 university and 12 community hospitals). Follow-up was conducted for the next 55 months. The percentage of patients older than 80 years (16%) was between the values for Eastern and Western countries. In patients younger than 55 years, a female predominance was observed (male/female ratio 0.70:1 vs. 1.29:1; p < 0.001). Female patients had higher platelet counts (160 × 109/l vs. 111 × 109/l; p < 0.001). Patients exposed to chemicals were younger than patients without such exposure; their median age at MDS diagnosis was 66 vs. 70 years (p = 0.037). Smokers had significantly lower hemoglobin concentrations (8.6 vs. 9.1 g/dl; p = 0.032) and lower platelet counts (99 × 109/l vs. 137 × 109/l; p < 0.001) than nonsmokers. We provide the first description of the characteristics of Polish MDS patients. Females predominated in the group aged <60 years and they had higher platelet counts. The course of the disease is affected by toxic exposure and smoking.

Promising results from cyclophosphamide based immunosuppression therapy of thrombotic thrombocytopenic purpura.

PURPOSE: Thrombotic thrombocytopenic purpura is a rare disease. Therefore, the small numbers of patients in trials results in statistically weak evidence supporting treatment guidelines. The aetiology of this disease is based on a deficiency of metalloproteinase 13 (ADAMTS-13), which leads to the creation of von Willebrand factor polymers and platelet microthrombosis in small vessels. Treatment relies on plasma exchange. Immunosuppression based on cyclophosphamide is not recommended in current guidelines. The aim of this study was to assess the early and long-term effects of treatment, and to evaluate therapy prognostic factors. MATERIAL AND METHODS: This was a retrospective study of 10 patients hospitalized 14 times due to new or recurrent onset of TTP. Currently recommended treatment was used in all cases, including total plasma exchange (range 0.5-2 plasma volume). The volume of exchange plasma was 24.6 L (mean) over 20 days (median). All patients received glucocorticosteroids. Immuno-uppression (based on cyclophosphamide in 7 cases) was utilized in 70% of patients (9 patients). RESULTS: Of all 11 patients 9 (70%) survived and achieved remission. Fifty percent of patients stayed in long-lasting remission. Average follow-up time was 36 months (median 14.5 months, range 10 days to 108 months). Factors improving the chance of remission were: age below 55 years (p < 0.05), no tachycardia on admission to hospital (p < 0.001), and immunosuppression based on cyclophosphamide (p = 0.032). CONCLUSIONS: Presence of tachycardia on TTP onset and age above 55 years reduce the survival and remission rate. Remission from TTP is suggested to be caused by immunosuppression based on cyclophosphamide.

[Kidney protection therapy in acute limb ischemia]. / Leczenie nefroprotekcyjne w ostrym niedokrwieniu konczyn dolnych.

Acute limb ischaemia is relatively frequent in the population (800:1 million, with about 1000 cases per year in Zachodniopomorskie province) and is a life-threatening condition due to significant mortality (about 15%) and a high percentage of amputation (up to 25%). Early death is mainly caused by metabolic disorders associated with reperfusion syndrome following surgical revascularisation. Muscle injury caused by rhabdomyolysis leads to acute renal failure, cardiopulmonary insufficiency and generalised inflammatory reaction. Prompt treatment according to the current recommendations, including extensive fasciotomy and intensive and early nephroprotective and renal replacement therapy, offers the only chance to reduce early mortality in patients suffering from this disease. Differences in approach to the problem of renal replacement therapy presented by nephrologists/internists and surgeons are frequent and do not improve treatment outcome. The aim of this paper is to establish a standard consensus between the approach of the vascular surgeon, nephrologist and internist to achieve the best possible treatment outcomes in patients with acute limb ischaemia.

[Gastric non-Hodgkin's lymphoma--clinical symptoms and diagnostic problems]. / Chloniaki nieziarnicze z pierwotna lokalizacja w zoladku--objawy kliniczne i trudnosci w rozpoznaniu.

INTRODUCTION: Gastric lymphoma takes 70% of lymphomas in gastric tract. Lack of characteristic symptoms and histological changes makes these disease difficult to recognize. The aim of the study was to search for specific constellation of the symptoms due to validation of diagnostic standards. MATERIAL AND METHODS: Retrospective analysis of clinical data for the group of 64 patients treated during 10 years in Hematology Department of Pomeranian Medical University in Szczecin. RESULTS: Recognition of gastric lymphoma in 80% was based on gastrocopy and histopatology examination. Gastrectomy was useful in 14 cases. Classic Ultrasound Abdomen Examination confirmed changes in 40%. Epigastic pain was raported as the most common symptom (54 from 64 patients). Systemic symptom appears in 34/64 patients (usually the loss of the body mass). CONCLUSIONS: 1. Clinical symptoms of non-Hodgkin's lymphoma in gastric localization are not specific. Epigastric pain, nausea and body mass lost are the symptoms the most often reported and physical symptoms do not reflect in systemic disease. 2. The standard of examination should consist of the transesophageal sonography (EUS) completed with multiple biopsy of gastric membrane and Hp tests.

[Latent chronic kidney disease in the material of the Department of Vascular Surgery, Pomeranian Medical University in Szczecin. An important clinical problem]. / Utajona przewlekla choroba nerek w materiale Kliniki Chirurgii Naczyniowej Pomorskiego Uniwersytetu Medycznego w Szczecinie. Istotny problem kliniczny.

INTRODUCTION: The percentage of patients with diagnosed chronic renal failure is many times smaller than the percentage of the latent disease. The rate of cardiovascular complications in latent kidney disease is significantly higher. The aim of this work was to determine the percentage of patients with renal failure among patients with peripheral atherosclerosis treated at our Department and to study rate (GFR) below the influence of reduced glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 on the risk of early complications after vascular surgery. MATERIAL AND METHODS: A retrospective analysis of 1096 patients was done. 652 patients were operated, 321 underwent endovascular procedures, including angiography, antiglobulin test (PTA), and fibrinolysis, and 123 were conservatively treated. There were no significant differences between these groups as regards biochemical parameters prior to treatment. RESULTS: Approximately 2% of patients presented with chronic renal failure at admission. However, GFR in more than 30% (370) of them was lower than 60 mL/min/1.73 m2. The incidence of myocardial infarction and pneumonia was more than three-fold greater in patients with reduced GFR (1.89 vs. 0.55, p = 0.042; 4.59 vs. 1.38, p = 0.0017, respectively). The incidence of gastrointestinal bleeding increased more than 18 times (3.78 vs. 0.28, p = 0.00002) and the incidence of stroke increased six times (2.43 vs. 0.41, p = 0.0032) in these patients. CONCLUSIONS: Latent renal failure is present in more than one-third of patients treated for peripheral atherosclerosis. GFR below 60 mL/min/1.73 m2 is associated with a higher risk of cardiovascular complications and postoperative gastrointestinal bleeding. Glomerular filtration rate should be routinely calculated at admission to hospital.

[Early death in vascular surgery: an ongoing prognostic problem]. / Wczesny zgon w chirurgii naczyniowej. Aktualny problem prognostyczny.

INTRODUCTION: Prediction of complications in surgery is commonly done. There are conflicting reports concerning the usefulness of risk scales (P-POSSUM, APACHE, SAPS, ASA, Goldman, etc.) in vascular surgery. We decided to take a fresh look at preoperative risk factors of early death in the context of the usefulness of some parameters which have not been included in existing risk calculators. MATERIAL AND METHODS: The study group consisted of 1270 patients treated at the Department of Vascular Surgery, General Surgery, and Angiology, Pomeranian Medical University in Szczecin, during one year. METHOD This was a prospective non-randomized study. All data recorded at admission and data from P-POSSUM, ASA, Goldman, and ECOG-Zubroda-WHO scales were analyzed. Statistics were done with discriminant, multivariate, and logistic tests. RESULTS: There were 42 early deaths in the group. The following independent risk factors were involved in early death: ASA > 2 (OR = 18.31), persistent atrial fibrillation (OR = 5.75), leukocytosis (OR = 13.31), glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 (OR = 5.78), systemic inflammatory response syndrome (SIRS) (OR = 11.36), emergency admission (OR = 38.62), critical limb ischemia (OR = 4.87), acute limb ischemia (OR = 8,98), abdominal aortic aneurysm (OR = 4.4), and ruptured aortic aneurysm (OR = 10.59). Logistic regression exposed the influence of five factors: ASA III, ASA IV, persistent atrial fibrillation, leukocytosis, GFR < 30 mL/kg/1.73 m2, and ruptured aortic aneurysm. The P-POSSUM calculator was found to be an accurate predictor of early death although the predicted death rate was insignificantly higher than the observed rate. CONCLUSION: Risk scales of early death currently used in vascular surgery need to be "refreshed". Creation of the Polish National Vascular Surgery Register seems to be unavoidable.

[Primary gastric non-Hodgkin's lymphoma: clinical findings and prognostic factors]. / Chloniaki nieziarnicze z pierwotna lokalizacja w zoladku--analiza kliniczna i czynniki rokownicze.

PURPOSE: This work was undertaken to determine the clinical course and prognostic factors in patients with primary gastric non-Hodgkin's lymphoma (NHL). MATERIAL AND METHODS: 64 patients were enrolled, including 26 females and 38 males, aged 22 to 80 years. The diagnosis of primary gastric NHL was made on the basis of histopathologic examination of samples collected during gastroscopy in 50 or gastrectomy in 14 patients. A retrospective analysis was performed of the relationship between the outcome of treatment and age, gender, histological type of the lymphoma, clinical staging according to the original Ann Arbor classification and as modified by Stein and coworkers, functional status according to the ECOG scale, International Prognostic Index, type of lymphoma according to the classification of Kramer, and type of primary therapy. Survival probability was calculated according to Kaplan-Meier. RESULTS: The results are presented in figures and tables. CONCLUSIONS: 1. The clinical picture of primary gastric non-Hodgkin's lymphoma is unrevealing. Patients usually complain of epigastric pain, nausea, vomiting, and weight loss. Clinical symptoms are rarely typical of a systemic disease. 2. Age, gender, functional status, histological type of the lymphoma, and clinical stage do not correlate with treatment outcome and survival. 3. Gastrectomy as the primary method of treatment has no advantage over chemotherapy in terms of treatment outcome and survival.