The clinical impacts of the controlling nutritional status score on patients with Hodgkin lymphoma.

OBJECTIVE: The aim of the study was to evaluate the clinical importance and potential mechanisms of controlling nutritional status (CONUT) score as a prognostic tool for Hodgkin lymphoma (HL). PATIENTS AND METHODS: Diagnosed with HL, 307 patients were included in the study. Patients' demographic data, stages, B symptoms, extranodal involvement, presence of bulky disease, laboratory findings, treatments, treatment responses, nutritional status, and overall survival (OS) rates were evaluated from the hospital records. The primary endpoint of our study was to evaluate and classify newly diagnosed HL patients under the CONUT score. The secondary endpoint was to indicate any relationship between nutritional status, CONUT score, and other prognostic factors and OS. RESULTS: Of 307 patients (173 males, 134 females), the mean age was 41.58±16.26 (ranging between 18-82 years). The most common type of malignancy was nodular sclerosis (72.53%). To the receiver operating characteristic (ROC) curve analysis, the best cut-off point was 2.5 to predict mortality. Eigthy-five (27.7%) and 222 (72.3%) patients had ≥3 and ≤2 CONUT scores, respectively. Twenty-four (10.80%) and 23 (27.10%) cases were also mortal in the patients with ≤2 and ≥3 CONUT scores, respectively (p<0.001). Survival times were significantly lower in those with higher (≥3) CONUT scores (p<0.001) than among the other patients. CONCLUSIONS: Evaluation of nutritional status plays an important role in the response and survival of those with hematological malignancies. Malnutrition can reduce patients' tolerance to chemotherapy and increase the risk of secondary infections. In this study, undernutrition evaluated with the CONUT score was demonstrated to be a potential independent prognostic factor for OS in patients with HL.

Impact of revised EORTC/MSGERC 2020 criteria on diagnosis and prognosis of invasive pulmonary aspergillosis in patients with hematological malignancies undergoing bronchoscopy.

INTRODUCTION: The first consensus definitions for invasive fungal diseases (IFD) were published in 2002. Advances in diagnostic tests and a clear need for improvement in certain areas led to a revision of these definitions in 2008. However, growing data on Aspergillus galactomannan (GM) thresholds and the introduction of new polymerase chain reaction-based diagnostic tests resulted in a further update by EORTC and Mycoses Study Group Education and Research Consortium (MSGERC) in 2020. Compared to the 2008 version, the 2020 EORTC/MSGERC criteria have stricter definitions, especially regarding GM levels, which should lead to improved specificity. Thus, our study aimed to evaluate diagnostic changes, based on GM levels, resulting from these new definitions and ascertain the impact of the new classification on mortality rates. METHOD: Patients hospitalized in a single tertiary care center with hematologic malignancies and undergoing bronchoscopy for suspected IPA between April 2004 and December 2019 were included in this retrospective study. RESULTS: The study population consisted of 327 patients with 31 patients (nine patients with proven IPA and 22 patients with no IPA) excluded from the study. 194 patients were classified as probable IPA cases according to 2008 EORTC/MSG criteria. However, 53 (27.3%) of these patients were re-classified as possible IPA according to 2020 EORTC/MSGERC criteria, due to novel galactomannan cut-off levels. Compared to re-classified possible IPA patients, those remaining in the probable IPA category experienced a higher incidence of septic shock (34.0% vs 16.9%, p=0.02), and required more non-invasive (12.0% vs 0.0%, p=0.004) and invasive (44.6 vs 24.5%, p=0.01) mechanical ventilation. There was a higher in-hospital mortality rate in probable IPA patients than in the re-classified possible IPA group (42.5% vs 22.6%, p=0.01). Patients reassigned to possible IPA had similar underlying diseases, radiological features and prognosis to patients already classified as possible IPA. Independent risk factors for mortality were classification as probable IPA according to 2020 EORTC/MSGERC criteria, lack of remission from hematologic malignancy, and number of nodules in Thorax CT. CONCLUSION: The use of 2020 EORTC/MSGERC criteria resulted in a 27.3% significant reduction in probable IPA diagnoses and created a more homogeneous category of patients with respect to treatment response, prognosis and mortality. Therefore, 2020 EORTC/MSGERC criteria afford more reliable mortality prediction than 2008 EORTC/MSG criteria.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

Brentuximab vedotin for relapsed or refractory Hodgkin lymphoma: experience in Turkey.

Current treatment modalities can cure up to 70-80 % of patients with classical Hodgkin lymphoma. Approximately, 20-30 % of patients require further treatment options. Brentuximab vedotin has been approved for the treatment of relapsed and refractory Hodgkin lymphoma. In the present study, we report the experience with brentuximab vedotin as single agent in 58 patients with relapsed or refractory Hodgkin lymphoma. The objective response rate was 63.5 % with 13 complete responders (26.5 %) among 49 patients evaluated at the early phase of treatment (2-5 cycles). Upon treatment prolongation (≥6 cycles), 37 patients achieved a final objective response rate of 32.4 % with 21.6 % of complete and 10.8 % of partial response. Overall survival at 12 months was 70.6 %, and progression-free survival at 12 months was 32.8 %. Median overall survival could not be reached and median progression-free survival was 7 months. While the median duration of response was 9 months in the whole cohort, it was 11.5 months in the complete responders. Complete response rates in patients treated with >3 chemotherapy regimens before brentuximab vedotin were significantly lower (p = 0.016). Fourteen patients were subsequently transplanted. In conclusion, brentuximab vedotin provided a bridge to transplantation in approximately one quarter of the patients. The declining response rates during the course of treatment suggest that transplantation should be implemented early during brentuximab vedotin treatment.

Neonatal outcomes of pregnancy complicated by idiopathic thrombocytopenic purpura.

OBJECTIVE: The aim of this study was to determine the factors associated with the prognosis of newborns born to mothers with idiopathic thrombocytopenic purpura (ITP), and to compare the infants with/without thrombocytopenia in terms of maternal and neonatal characteristics. STUDY DESIGN: We reviewed the charts of 29 parturients with ITP and their newborns who were born between January 1998 and December 2008. RESULT: A total of 16 (55%) gravidas had been diagnosed with ITP before pregnancy and 13 (45%) were diagnosed during pregnancy. Thrombocytopenia was observed in 21 gravidas. In total, 17 (58%) gravidas received treatment to increase the platelet count. The majority of deliveries (72.5%) were vaginal. The infant platelet counts at birth ranged from 20 to 336 x 10(9) per liter. None of the neonates had complications attributable to the mode of delivery. Normal platelet counts were determined in 15 newborns, whereas 14 infants had thrombocytopenia at birth. Three (10.3%) neonates had mild, four neonates (13.7%) had moderate and seven neonates (24.1%) had severe thrombocytopenia. The age of the mothers having infants with thrombocytopenia was significantly higher (30+/-5.3 vs 25.3+/-3.8 years), most of the infants (10/14 (71%)) were males (P<0.05). CONCLUSION: Pregnancy complicated with ITP generally has a good outcome. Although ITP in pregnancy carries a low risk, careful observation is required for the newborn of gravidas with ITP even when the infant has no bleeding complications at delivery, and infants may require treatment for thrombocytopenia.

Tumor lysis syndrome as a contributory factor to the development of reversible posterior leukoencephalopathy.

INTRODUCTION: Reversible posterior leukoencephalopathy syndrome (RPLS) is a recently described clinical and radiological entity comprising headache, seizures, altered level of consciousness and visual disturbances in association with transient posterior cerebral white-matter abnormalities. METHOD: We report a young woman with Burkitt's lymphoma who developed RPLS after combined chemotherapy administered during the tumor lysis syndrome. RESULTS: The symptoms in this patient fitted well with those of RPLS; they included abrupt alterations in mental status, seizures, headache, visual changes and characteristic neuroradiological findings. She was given further combination chemotherapy without any neurological complications, at which time she had already recovered from both RPLS and tumor lysis syndrome. CONCLUSION: Although many etiological factors have been reported in the development of RPLS, the underlying mechanism is not yet well understood. With prompt and appropriate management, RPLS is usually reversible, and chemotherapy can be continued after complete recovery from RPLS. We suggest that tumor lysis syndrome should be considered as a contributory factor to the development of RPLS in patients for whom treatment with combined chemotherapy for hematological malignancies is planned.

Bacillus spp. among hospitalized patients with haematological malignancies: clinical features, epidemics and outcomes.

Between April 2000 and May 2005, 350 bacteraemic episodes occurred among patients treated in our haematology unit. Two hundred and twenty-eight of these episodes were caused by Gram-positive pathogens, most commonly coagulase-negative staphylococci and Staphylococcus aureus. One hundred and twenty-two episodes were due to Gram-negative pathogens, with a predominance of Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa. Bacillus bacteraemias constituted 12 of these episodes occurring in 12 patients, and accounted for 3.4% of all bacteraemic episodes. Of the 12 strains evaluated, seven were Bacillus licheniformis, three were Bacillus cereus and two were Bacillus pumilus. Seven episodes presented with bloodstream infection, three with pneumonia, one with severe abdominal pain and deterioration of liver function, and one with a catheter-related bloodstream infection. B. licheniformis was isolated from five patients who had been hospitalized at the same time. This outbreak was related to non-sterile cotton wool used during skin disinfection. B. cereus and B. licheniformis isolates were susceptible to cefepime, carbapenems, aminoglycosides and vancomycin, but B. pumilus isolates were resistant to all antibiotics except for quinolones and vancomycin. Two deaths were observed. In conclusion, Bacillus spp. may cause serious infections, diagnostic and therapeutic dilemmas, and high morbidity and mortality in patients with haematological malignancies. Both B. cereus and B. licheniformis may be among the 'new' Gram-positive pathogens to cause serious infection in patients with neutropenia.

Successful labor in the course of chronic lymphocytic leukemia (CLL) and management of CLL during pregnancy with leukapheresis.

We describe the successful management of a 30-year-old woman in the second trimester of her pregnancy with chronic lymphocytic leukemia (CLL) in stage IV by using only leukapheresis. We applied three sessions (courses) of leukapheresis throughout the pregnancy. The procedure did not have any significant adverse effect on the patient and the fetus. The patient gave birth vaginally to a healthy boy, weighing 3100 g, at 39 weeks of gestation. Seven months after delivery, Richter's syndrome developed in the patient. We conclude that leukapheresis may provide an alternative for palliative treatment to chemotherapy in pregnant patients with CLL. To our knowledge, this is the fourth reported case of CLL in pregnancy, and the first management of CLL during pregnancy with leukapheresis.

Idiopathic thrombocytopenic purpura in pregnancy: a single institutional experience with maternal and neonatal outcomes.

We observed 13 pregnant women of 70 females with idiopathic thrombocytopenic purpura (ITP) from January 1992 through September 2002. Thirteen mothers with ITP gave birth to twelve babies and two fetuses died. One of the pregnancies produced twins. Seven of the cases were diagnosed with ITP before pregnancy and six during pregnancy. One of the thirteen pregnancies was complicated by preeclampsia, one by ablatio placentae, and one by intrauterine death. Seven mothers received corticosteroid treatment, four high-dose immunoglobulin therapies, and one underwent splenectomy in the second trimester of gestation. At the time of delivery six mothers had normal platelet counts and seven had low platelet counts. Nine deliveries were by vaginal route and four were by cesarean section. Eleven infants were born with normal platelet counts and one was thrombocytopenic at the time of delivery. No infant showed any clinical signs of hemorrhage and there were no neonatal complications. Two fetuses died; one of them because of ablatio placentae and the other was intrauterine dead. In conclusion, ITP in pregnancy requires the management of two patients, the mother and her baby; hence, the close collaboration of a multidisciplinary group composed of a hematologist, obstetrician, anesthesiologist, and neonatologist is essential.

99mTc-MIBI scintigraphy in untreated stage III multiple myeloma: comparison with X-ray skeletal survey and bone scintigraphy.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) is a lipophilic agent that has been proposed as a useful tracer for the detection of disease sites in patients with multiple myeloma (MM). We performed a prospective study to determine the potential of 99mTc-MIBI imaging for the evaluation of the extent of primary disease in patients with advanced stage MM, compared with skeletal survey and bone scintigraphy. Twenty patients with advanced stage MM at initial diagnosis underwent whole-body 99mTc-MIBI imaging, together with contemporaneous skeletal survey and bone scintigraphy. The findings of 99mTc-MIBI imaging were correlated with the results of skeletal survey and bone scan. All 99mTc-MIBI scans were positive for the presence of active MM, whereas skeletal surveys were positive in 18 patients (90%) with osteolytic lesions. Bone scintigraphy demonstrated MM in only 15 patients (75%). In two patients with no detectable lesions on skeletal survey, 99mTc-MIBI imaging revealed uptake in the spine, corresponding to the abnormalities seen on magnetic resonance imaging (MRI). With respect to the localization of bone lesions, 99mTc-MIBI imaging was superior to bone scintigraphy in 15 patients (75%) and had concordant results with bone scintigraphy in four (20%). 99mTc-MIBI imaging is a very sensitive imaging modality for the identification of the extent of disease in patients with advanced MM. It is clearly superior to bone scintigraphy and complements the results of skeletal survey by finding additional disease sites. Hence, in active MM patients, 99mTc-MIBI imaging has the potential to detect bone marrow disease that cannot be detected by skeletal survey and bone scintigraphy.

Successful treatment of acquired haemophilia with prednisolone therapy.

Acquired hemophilia is a rare, life threatening coagulopathy in adults caused by the development of autoantibodies against to factor VIII. No general consensus exists on the best therapeutic approach. We report here a case that presented with extensive cutaneous and mucosal bleedings due to factor VIII inhibitors and treated successfully with steroid therapy alone but complicated with a life threatening thromboembolic attack during her follow up. In conclusion, corticosteroids are "cost effective therapy" associated with high inhibitor elimination rates and although recurrence of inhibitor in a patient with factor VIII inhibitor is an expected clinical situation thrombosis risk should also be considered.

Multiple myeloma in the region of Bursa, Turkey: a retrospective analysis.

We evaluated the clinical and laboratory features of multiple myeloma in our patients and reviewed the factors that affected their survival. The study included 36 patients (12 women and 24 men) with multiple myeloma whom we followed up until death between October 1978 and June 1995. The age range was 34 to 75 years (mean age, 53.9). The chief complaints on admission were lumbar pain and pain in the extremities (77.8%) and generalized weakness (61.1%). The most common laboratory findings were severe anemia (hemoglobin < 8.0 g/dl) (50%), elevated erythrocyte sedimentation rate (75%), monoclonal spike in the serum protein electrophoresis (44.4%), and lytic skull lesions (72.2%). Twenty-three (64%) patients had a monoclonal IgG, 9 (25%) had IgA, 1 had IgD, 2 had light chain disease, and 1 was nonsecretory. Localized plasmacytoma was detected in 4 patients and 4 patients had amyloidosis in rectal and gingival biopsies. According to the Durie-Salmon staging system, 2 patients were in stage 1, 8 were in stage 2, and 26 were in stage 3. The mean survival was 31.4 +/- 4.3 months (range: 1 to 96). The 5-year survival rate was 11%. Sex, age at diagnosis, stage of the disease, hemoglobin level, platelet count, level of serum calcium, creatinine, serum paraprotein, and type of paraproteinemia were tested as prognostic parameters. We could not establish a statistically meaningful effect of these parameters on survival time. The first and second most common causes of death were renal failure and infection, respectively.

Second primary cancer due to radiotherapy and chemotherapy.

Cancer patients are treated successfully with chemotherapy, radiotherapy, or a combination of both. However, many agents used in cancer chemotherapy as well as ionizing radiation are known carcinogens. The long survival of cancer patients treated successfully for their primary cancer made possible the observations of late effects of radiotherapy and chemotherapy and, in particular, the occurrence of second primary cancers. In this report we review the cases of five patients with second primary malignancies and wish to emphasize the importance of a thorough follow-up of patients treated successfully for and possibly cured of a primary cancer.