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.

Secondary Hemophagocytic Syndrome in a Patient with Plasma Cell Myeloma and CNS Involvement Treated with Lenalidomide.

We present an extremely rare case report of a 29-year-old multiple myeloma patient with central nervous system involvement and secondary hemophagocytic lymphohistiocytosis (HLH). We observed that HLH was presumably triggered by the immunomodulatory drug-lenalidomide. HLH is frequently misdiagnosed or underdiagnosed. As HLH requires immediate treatment, our report emphasizes the need to consider HLH in the differential diagnosis when the condition of a patient receiving chemotherapy rapidly deteriorates and an infectious etiology is excluded. We furthermore discuss the pathogenesis of HLH, with particular emphasis on drugs affecting the immune system as well as possible therapeutic strategies.

Protozoan Intestinal Parasitic Infection in Patients with Hematological Malignancies.

The aim of this study was to evaluate the frequency of gastrointestinal protozoan infection in patients with hematological malignancies (HMs) undergoing intensive hemato-oncological treatment and to determine the influence of certain biological factors on the incidence of intestinal parasite infection. Stool samples were collected from hematological malignancy patients (n = 50) hospitalized at the Department of Hematology and Transplantology of the Pomeranian Medical University in Szczecin. The control group consisted of 50 healthy participants. We used a direct smear examination and a commercial immunoenzymatic test. Intestinal protozoans were detected in 16% of patients with hematological malignancies and in 6% of individuals in the control group. In stool samples from patients with HM, cysts of Giardia intestinalis (2%), oocysts of Cryptosporidium spp. (10%), vacuolar forms of potentially pathogenic Blastocystis spp. (2%), and cysts of nonpathogenic Entamoeba coli (2%) were found. Cryptosporidium spp. and Giardia intestinalis coproantigens were detected in 5 (10%) and 1 (2%) patients with HM, respectively. In three participants from the control group, vacuolar forms of Blastocystis spp. were found. In the patients with HM, a significantly higher prevalence of intestinal parasite infection was found in individuals working in the garden without protective gloves and those in contact with animals. In patients with hematological malignancies, intestinal parasites should be excluded, even during intensive chemotherapy treatment.

Case of Patient with AML with Complex Karyotype including Ultra-Rare t(4;8)(q32;q13), t(4;11)(q21;p15) and Familial Aggregation of Myeloid Malignancies.

We present a unique case of a young woman with acute myeloid leukemia (AML) with complex karyotype. The presence of the t(4;11)(q23;p15) is extremely rare in myeloid leukemias, while t(4;8)(q32;q13) has not yet been described in any leukemia reference. Another interesting issue is the familial aggregation of myeloid malignancies and worse course of the disease in each subsequent generation, as well as an earlier onset of the disease. Our report emphasizes the need for thorough pedigree examination upon myeloid malignancy diagnosis as there are relatives for whom counseling, gene testing, and surveillance may be highly advisable.

Hodgkin Lymphoma as a Secondary Neoplasm During Therapy for Chronic Myeloid Leukaemia: Case Report and Review of the Literature.

INTRODUCTION: Incidences of chronic myeloid leukaemia (CML) after treatment of Hodgkin lymphoma (HL) are well described. Here, we report a case of secondary HL in a patient with CML treated with dasatinib as a third-line treatment. PATIENT INFORMATION: A 64-year-old male was diagnosed with CML and initially treated with imatinib and then with nilotinib due to resistance. Finally, the patient experienced cardiovascular complications, and dasatinib was introduced. After 19 months of treatment, the patient experienced enlargement of lymph nodes that formed packs on the neck. INTERVENTIONS: Based on histopathological examination of the lymph nodes, a diagnosis of classical Hodgkin lymphoma - mixed cellularity was established. The patient was successfully treated with 4 cycles of AVD (adriamycin, vinblastine, dacarbazine) chemotherapy. OUTCOMES: Complete metabolic remission of Hodgkin lymphoma is currently sustained, and the molecular response to dasatinib at a reduced dose of 50 mg daily corresponds with a deep molecular response. CONCLUSION: In this report, we demonstrate the efficacy and safety of the combination of dasatinib and AVD regimens in coexisting CML and HL. This case report emphasizes the importance of insightful evaluation and differential diagnosis in cases of lymphadenopathy during CML treatment.

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.

Chemotherapy and echocardiographic indices in patients with non-Hodgkin lymphoma: the ONCO-ECHO study.

The cardiotoxicity of chemotherapy (CTx) for non-Hodgkin's lymphomas is not well recognized. In order to facilitate individual risk counseling for patients, we analyzed the effect of CTx on echocardiographic indices in regard to clinical data in patients treated for non-Hodgkin's lymphoma (NHL). A prospective multicenter ONCO-ECHO trial included 67 patients with NHL (45 patients with DLBCL (diffuse large B cell lymphoma) and 22 with non-DLBCL). Patients received standard CTx, primarily R-CHOP, CHOP, R-COP and COP regimens. Clinical data and echocardiographic indices were obtained at baseline, 3-, 6- and 12-month follow-up. The primary end point representing CTx cardiotoxicity was defined as a ≥ 10% decrease in the left ventricular ejection fraction (LVEF) during 12-month observation. In a 12-month follow-up five (7.5%) deaths occurred, while no clinical manifestations of heart failure were reported. There was an increase in left ventricular end-systolic diameter (p = 0.002) and E/e' index (p = 0.036) in 12-month observation. Preexisting coronary artery disease was associated with significant decrease in the ΔLVEF (p = 0.008), increase in ΔLVEDV (p = 0.03) and ΔLVESV (p = 0.02) and increase in the Δ left atrium diameter (p = 0.02); while history of arterial hypertension was related to significant decrease in the ΔLVEF (p = 0.039), diabetes mellitus was related to significant increase in the ΔE/e' index (p = 0.002). The primary end point was reported in ten (14.9%) patients. There were no independent risk factors for cardiotoxicity in the study population. Chemotherapy administered to NHL patients may induce dilatation and impaired LV diastolic function. Standard cardiovascular risk factors may predispose patients to negative LV remodeling.

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo-HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: a retrospective, multicenter Polish Adult Leukemia Group study.

The importance of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999-2008. The Mantel-Byar approach was used to assess allo-HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo-HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41-60. The CIR demonstrated that allo-HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo-HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41-60. The allo-HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis.

Demodex folliculorum and Demodex brevis in healthy and immunocompromised patients.

PURPOSE: To examine the proportion of Demodex folliculorum and D. brevis in the eyelashes of healthy and immunocompromised patients. METHODS: Eyelashes were taken from 95 patients at the Pomeranian Medical University, Clinic of Haematology, and from 1091 healthy controls. RESULTS: Demodex folliculorum and D. brevis were found in 22.9% of controls and in 20% of immunocompromised patients. In neither the control group nor the immunocompromised patients did we observe a correlation between the proportion of symptoms of blepharitis and the presence of Demodex spp. - symptoms including burning sensations, loss of eyelashes, sensitivity to light, smoke and dust, dacryorrhea (excessive flow of tears), and foreign body eye sensation. A correlation between itching eyes and Demodex spp. infection was found only in the control group. A correlation between the proportion of cylindrical dandruff in eyelashes and the occurrence of Demodex spp was found in both the control group and immunocompromised patients. CONCLUSION: Proportions of D. folliculorum and D. brevis, and also symptoms of blepharitis were similar in the control group and immunocompromised patients. Immunosuppression did not seem to increase the rate of Demodex spp. infection.

Case report: rare case of infiltration of small lymphocytic B-cell lymphoma in the thyroid gland of female patient with B-cell chronic lymphocytic leukemia (CLL-B/SLL-B).

The article presents a case of 57-year-old woman with the infiltration of rare small lymphocytic B cell lymphoma in the thyroid gland. Initially, the patient was followed-up due to chronic lymphocytic B-cell leukemia diagnosed on the basis of histopathological examination of cervical lymph node. Eight months later, general symptoms occurred along with lymphocytosis and exacerbation of lesions in lymph nodes, and therefore, chemotherapy was started according to COP regimen. After four chemotherapy cycles, further progression of the disease was observed during chemotherapy. Computed tomography (CT) performed at that time showed generalized lymphadenopathy and the presence of an irregular area in left thyroid lobe. On palpation, the thyroid was asymmetrical, with enlarged left lobe and palpable lymph node packages on the left side of the neck. The levels of thyroid hormones and anti-thyroid antibodies were normal. Ultrasound examination of the thyroid gland showed non-homogeneous hypoechogenic structure of the left lobe and complete focal remodeling. Cytological examination of left-lobe lesion obtained during fine needle aspiration biopsy showed multiple small lymphoid cells, suggestive of small lymphocytic lymphoma. To confirm this diagnosis, flow cytometry of the biopsy material sampled from the left lobe was performed showing B cellimmunophenotype: CD19+/CD20+/CD22 dim/FMC-7, CD23+/CD5+, sCD79b-+, CD38-, CD10-, kappa and lambda-/weak reaction. The results of flow cytometry of the thyroid bioptate and blood were nearly identical, confirming leukemic nature of the infiltration in left thyroid lobe. Cytogenetic findings included the presence of 17p deletion (TP53 gene). The patient received immunochemotherapy with alemtuzumab. The progression of the disease occurred in the sixth week of therapy. The treatment was discontinued after 8 weeks due to worsening of patient's general status. The patient died 15 months after the diagnosis.

Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study.

PURPOSE: The goal of this study was to evaluate whether the addition of a purine analog, cladribine or fludarabine, to the standard induction regimen affects the outcome of adult patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: A cohort of 652 untreated AML patients with median age 47 years (range, 17 to 60 years) were randomly assigned to receive one of three induction regimens: DA (daunorubicin plus cytarabine), DAC (DA plus cladribine), or DAF (DA plus fludarabine). Postremission treatment was the same for all arms. RESULTS: Complete remission rate in the DAC arm was higher compared with the DA arm (67.5% v 56%; P = .01) as a consequence of reduced incidence of resistant disease (21% v 34%; P = .004). There was no significant difference in early outcome between the DAF and DA arms. The probability of overall survival was improved for the DAC arm (45% ± 4% at 3 years) compared with the DA arm (33% ± 4%; P = .02), and leukemia-free survival was comparable. Long-term outcome did not differ significantly for the comparison of the DAF and DA arms. A survival advantage of the DAC arm over the DA arm was observed among patients age 50 years or older (P = .005), those with initial leukocyte count above 50 × 10(9)/L (P = .03), and those with unfavorable karyotype (P = .03). DAF revealed a significant advantage over DA in patients with adverse karyotype (P = .02). CONCLUSION: The addition of cladribine to the standard induction regimen is associated with increased rate of complete remission and improved survival of adult patients with AML.

[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.

The early reduction of leukemic blasts in bone marrow on day 6 of induction treatment is predictive for complete remission rate and survival in adult acute myeloid leukemia; the results of multicenter, prospective Polish Adult Leukemia Group study.

The aim of this study was to prospectively evaluate the impact of early bone marrow response on complete remission (CR) rate and long-term outcome in adults with acute myeloid leukemia. Bone marrow cytology was assessed on day 6 of induction treatment in 164 patients, revealing the presence of ≥5% blasts in 61 cases. In this subgroup the CR rate was significantly lower compared to the remaining patients (P < 0.00001) resulting in decrease of the overall survival (P = 0.002). Persistence of ≥5% blasts in bone marrow on day 6 of induction is an easily available surrogate marker to be used for treatment decisions.

Infectious complications in patients with acute myeloid leukemia treated according to the protocol with daunorubicin and cytarabine with or without addition of cladribine. A multicenter study by the Polish Adult Leukemia Group (PALG).

OBJECTIVES: The addition of cladribine to the standard regimen consisting of daunorubicin and cytarabine has been reported to increase the efficacy of induction therapy in acute myeloid leukemia (AML). The goal of this study was to determine the effect of this modification on the incidence and spectrum of infectious complications. METHODS: Case report forms of 309 patients with newly diagnosed AML who had been enrolled in the prospective, randomized 'DAC-7 vs. DA-7' trial were reviewed. The frequency, etiology, localization, severity, and outcome of infections were compared for patients receiving only daunorubicin and cytarabine (DA-7) and those additionally treated with cladribine (DAC-7). RESULTS: A total of 443 febrile episodes were reported with no significant difference between the treatment groups. A trend towards a higher frequency of bacteremias was observed among DA-7 patients compared to those in the DAC-7 group (31% vs. 21%; p=0.08). The treatment arms did not differ in terms of the distribution of the isolated Gram-positive, Gram-negative, fungal, and viral organisms. However, when bacteremias were considered, Gram-positive blood cultures tended to be more frequent in the DA-7 compared to the DAC-7 group (16% vs. 8.5%; p=0.07). This difference reached statistical significance when major blood bacteremias were analyzed separately (13% vs. 5%; p=0.02). Complete recovery from infections was observed in the majority of patients across both treatment arms and no significant difference was noted regarding infection-related mortality. CONCLUSIONS: The addition of cladribine to standard induction chemotherapy has no impact on the incidence and spectrum of infectious complications in newly diagnosed AML patients.

Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome--Polish Adult Leukemia Group (PALG) pilot study.

In 1992-1993, synergistic interaction of ribonucleotide reductase inhibitors (fludarabine, cladribine) and cytarabine (Ara-C) increasing Ara-CTP concentration in myeloblasts was proved. Based on these findings and encouraging results of the addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early outcome. The DAF regimen consisted of daunorubicine 60 mg m(-2) day(-1) iv on days 1-3 and fludarabine 25 mg m(-2) day(-1) iv on days 1-5 given before cytarabine 200 mg m(-2) day(-1) in ci on days 1-7. Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study between September 2003 and August 2004. Achieved response rate in the whole study population was 56%; n = 16 patients with complete remission (CR), and n = 3 patients with partial remission (PR). Fifteen of 16 patients achieved CR after the first course of therapy. Only 9% of total population died before the assessment of remission. All patients developed severe neutropenia. Serious infections were observed in 47% of the cases. Severe thrombocytopenia was observed in 72% of the patients. All patients required substitution of platelet concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis, vomiting were of low frequency. Liver, kidney, or circulatory failure, diarrhea, or polyneuropathy were not observed. The probability of overall survival (OS) for 1 year for the whole study population (34 patients) and the group of 16 patients in CR was: 44% (95% confidence interval [CI] 36-52%) and 69% (95% CI 55-83%), respectively. The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI 22-54%). Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable toxicity and early efficacy.

Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial.

Cladribine (2-chlorodeoxyadenosine, 2-CdA) treatment-associated infections may shorten potentially long-term survival in hairy cell leukemia (HCL). In search of the optimal mode of 2-CdA administration, 132 patients with untreated HCL were randomized to receive either standard 5-day 2-CdA protocol or a novel schedule of 6 weekly 2-CdA infusions suggested to be less toxic. Analysis of treatment response confirmed similar complete remission rates, overall response rates, progression-free survival, and overall survival in both 2-CdA protocols. However, we did not observe lower toxicity in the weekly schedule. Of special interest, no significant differences were found in the rate of grade 3/4 infections (18% for daily and 26% for weekly protocol, difference -8.2%; 95% confidence interval [CI] -23.2% to 6.9%; P = .28) and the rate of septic deaths (3% for daily and 2% for weekly protocol, difference 1.4%; 95% CI -4.3% to 7.0%; P = .64). In conclusion, HCL treatment with weekly 2-CdA infusions is equally effective but no safer than the standard 5-day 2-CdA protocol.

Comparison of cladribine plus prednisone with chlorambucil plus prednisone in patients with chronic lymphocytic leukemia. Final report of the Polish Adult Leukemia Group (PALG CLL1).

BACKGROUND: We previously published an early report of a randomized, multicenter trial on the efficacy and toxicity of cladribine (2-CdA) + prednisone (P) compared with chlorambucil (Chl) + P in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia. Here we present the final report of this study. MATERIAL/METHODS: Of 229 patients, 126 received 2-CdA+P and 103 Chl+P. Patients with no response or progression after three courses or who relapsed earlier than 12 months after completing one treatment were switched to the other. Patients who relapsed later were retreated with the same schedule as before. RESULTS: Thirty-three patients were retreated with 2-CdA+P and 19 with Chl+P. Overall response (and complete response) rates were 35% (6%) and 47% (16%), respectively. In 50 patients initially treated with Chl+P and then with 2-CdA+P, complete response (CR) was achieved in 12 (24%) and overall response (OR) in 32 (64%). In 28 patients originally treated with 2-CdA+P and then with Chl+P, CR in 1 (3%, p=0.01) and OR in 6 (21%, p=0.003) were obtained. We found no statistically significant difference in overall survival time in patients treated initially with 2-CdA+P and Chl+P aged 60 years (4.63 and 5.27 years, respectively, p=0.45), 60-70 years (3.29 and 3.14 years, p=0.79), and >70 years (1.53 and 1.93 years, p=0.11). CONCLUSIONS: 2-CdA+P is significantly more effective as a second-line treatment and re-treatment than Chl+P. However, we found a trend to longer survival in elderly patients treated with Chl+P.