CML in the very elderly: the impact of comorbidities and TKI selection in a real-life multicenter study.

Tyrosine kinase inhibitors (TKIs) have greatly improved chronic myeloid leukemia (CML) treatments, with survival rates close to the general population. Yet, for the very elderly, robust data remains limited. This study focused on assessing comorbidities, treatment approaches, responses, and survival for elderly CML patients. Our study was conducted on 123 elderly (≥ 75 years) CML patients across four centers in Israel and Moffitt Cancer Center, USA. The median age at diagnosis was 79.1 years, with 44.7% being octogenarians. Comorbidities were very common; cardiovascular risk factors (60%), cardiovascular diseases (42%), with a median age-adjusted Charlson Comorbidity Index (aaCCI) of 5. Imatinib was the leading first-line therapy (69%), while the use of second-generation TKIs increased post-2010. Most patients achieved a major molecular response (MMR, 66.7%), and half achieved a deep molecular response (DMR, 50.4%). Over half (52.8%) of patients moved to second-line, and nearly a quarter (23.5%) to third-line treatments, primarily due to intolerance. Overall survival (OS) was notably longer in patients with an aaCCI score below 5, and in patients who attained DMR. Contrary to expectations, the Israeli cohort showed a shorter actual life expectancy than projected, suggesting a larger impact of CML on elderly survival. In summary, imatinib remains the main initial treatment, but second-generation TKIs are on the rise among elderly CML patients. Outcomes in elderly CML patients depend on comorbidities, TKI type, response, and age, underscoring the need for personalized therapy and additional research on TKI effectiveness and safety.

Prevalence and Clinical Characteristics of Paraproteinemia Associated with Chronic Myeloid Leukemia.

INTRODUCTION: Data regarding the prevalence of paraproteinemia in patients with chronic myeloid leukemia (CML) are lacking. METHODS: To evaluate for the prevalence of paraproteinemia, we undertook this cross-sectional study among consecutive chronic-phase CML patients. Complete blood count, chemistry, immunoglobulins, serum-free light chains, serum-protein electrophoresis and immunofixation were collected. Further analyses evaluated whether various patient-, disease-, and treatment-related variables are associated with paraproteinemia. RESULTS: One hundred patients, median age 63.5 (IQR 48.1-72) years were recruited. Median time from CML diagnosis to enrollment was 6.3 (IQR 2.3-11.3) years. Monoclonal protein was detected in 8 patients (8%), diagnosed with smoldering multiple myeloma (SMM, n = 2) and low-risk monoclonal gammopathy of undetermined significance (MGUS, n = 6). Six patients were on tyrosine kinase inhibitor treatment, 2 were in treatment-free remission. The only covariate associated with paraproteinemia was the presence of anemia, albeit with borderline statistical significance in univariate analysis (p = 0.053) and when adjusted for age (p = 0.056). CONCLUSIONS: In this largest study so far describing the prevalence of paraproteinemia among CML patients, we found MGUS prevalence to be higher than the 3.2% expected prevalence in the general population above 50 years and a non-negligible prevalence of SMM (2%). Screening for paraproteinemia in CML patients, especially in the presence of anemia, should be considered.

Feasibly of CD24/CD11b as a Screening Test for Hematological Malignancies.

An estimated 1.24 million blood cancer cases occur annually worldwide, accounting for approximately 6% of all cancer cases. Currently, there are no standardized hematology cancer screening tests that are recommended for the general population. CD24 is a mucin-like cell surface molecule and P-selectin ligand, which plays a significant role in the maturation of B-lymphocytes and was found to be overexpressed in a number of hematological malignancies. Our primary aim was to assess the sensitivity and specificity of the CD24/CD11b-based blood test for the detection of hematological malignancies. Our cohort included 488 subjects with positive hematological cancer diagnosis (n = 122) and healthy subjects (n = 366). CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results demonstrated that the average levels of CD24/CD11b in healthy patients (21.7 ± 9.0) were statistically significantly lower compared to levels of CD24/CD11b in cancer patients (29.5 ± 18.7, p < 0.001). The highest levels of CD24/CD11b were found in multiple myeloma (39.1 ± 23.6), followed by chronic myeloid leukemia (33.0 ± 13.7) and non-Hodgkin lymphoma (32.3 ± 13.3). The test had an overall sensitivity for hematologic cancers of 78.5% (95% CI, 70.7-86.3%) and specificity of 80.2% (95% CI, 76.1-84.3%). In conclusion, our findings indicate the feasibility of a CD24/CD11b-based blood test as a screening test of hematological malignancies.

Skin biopsies in acute myeloid leukemia patients undergoing intensive chemotherapy are safe and effect patient management.

There is paucity of data regarding the diagnostic yield and safety of skin biopsies in patients with acute myeloid leukemia (AML), though skin eruptions are common in these patients. We evaluated 216 patients treated in our hemato-oncology unit at a tertiary medical center between 2007 and 2018 and identified 35 patients who underwent 37 skin biopsies. The majority of biopsies were performed during induction treatment for AML (n = 26, 70%), whereas the remainder of biopsies were done prior to induction initiation (n = 8, 22%) or during consolidation chemotherapy (n = 3, 8%). Pathology findings were inconclusive in 13 cases (35%), while diagnostic biopsies were positive for drug eruptions (24%), leukemia cutis (16%), infections (11%), reactive processes (8%) and Sweet syndrome (5.5%). In almost half of cases (16/37) tissue cultures were performed. Of those, only a quarter (4/16) were positive. Histopathology and tissue culture results altered immediate patient care in 3 cases (8%), yet information obtained from biopsies had potential to affect long term patient care in 8 additional cases (21.6%). Although most skin biopsies were performed while patients had severe thrombocytopenia and neutropenia, only one patient had a complication due to the biopsy (fever and local bleeding). With the limitation of a retrospective analysis, our study suggests that skin biopsies in patients treated for AML are relatively safe. Although biopsy results infrequently alter immediate patient management, long term effect on patient care expand the potential diagnostic yield of skin biopsies.

Management and Outcome of Venous Thrombosis in Patients with Myeloproliferative Neoplasms: Data from the Israeli MPN Working Group.

The BCR-ABL-negative myeloproliferative neoplasms (MPN) are associated with high incidence of venous thrombosis and a significant rate of recurrent events, but there is no consensus regarding their management. In this retrospective study, we analyzed 96 patients with MPN-related venous thrombosis. The index venous thrombosis occurred at a median age of 58 years (IQR 37-71), with 58% of the events involving unusual sites. Patients who were on antiplatelet agents at the time of index thrombosis tended to be older than patients who were not receiving antiplatelets at the time of index thrombosis. The majority of index thromboses occurring after the diagnosis of MPN had uncontrolled blood counts at the time of event and were not receiving antithrombotic agents. Following the thrombotic episode, 75% of patients received long-term anticoagulation. At a median follow-up of 3.4 years, the recurrence rate was 14%. Thrombophilia was significantly more prevalent among patients with recurrent thrombosis compared to patients without recurrence (p < 0.01). Patients who developed a recurrent event early were more likely to have thrombophilia (either inherited or antiphospholipid antibodies), and controlled blood counts, and were likely to receive anticoagulation at the time of recurrence compared to patients with later recurrences. Thrombophilia may contribute to venous thrombosis recurrence, especially early after the index venous thrombosis. Suboptimal anticoagulation and blood count control are factors associated with late venous thrombosis recurrence.

Neutrophil Extracellular Traps Are Increased in Chronic Myeloid Leukemia and Are Differentially Affected by Tyrosine Kinase Inhibitors.

Cardiovascular complications are increasingly reported with the use of certain tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML). We studied neutrophil extracellular trap (NET) formation in CML and evaluated the effect of TKIs on NET formation. Neutrophils isolated from treatment-naïve patients with CML showed a significant increase in NET formation compared to matched controls at baseline and after stimulation with ionomycin (IO) and phorbol 12-myristate 13-acetate (PMA). Expression of citrullinated histone H3 (H3cit), peptidyl arginine deiminase 4 (PAD4) and reactive oxygen species (ROS) was significantly higher in CML samples compared to controls. Pre-treatment of neutrophils with TKIs was associated with a differential effect on NET formation, and ponatinib significantly augmented NET-associated elastase and ROS levels as compared to controls and other TKIs. BCR-ABL1 retroviral transduced HoxB8-immortalized mouse hematopoietic progenitors, which differentiate into neutrophils in-vitro, demonstrated increased H3cit & myeloperoxidase (MPO) expression consistent with excess NET formation. This was inhibited by Cl-amidine, a PAD4 inhibitor, but not by the NADPH inhibitor diphenyleneiodonium (DPI). Ponatinib pre-exposure significantly increased H3cit expression in HoxB8-BCR-ABL1 cells after stimulation with IO. In summary, CML is associated with increased NET formation, which is augmented by ponatinib, suggesting a possible role for NETs in promoting vascular toxicity in CML.

Health-Related Quality of Life in Patients with Chronic Myeloid Leukemia Treated with First- Versus Second-Generation Tyrosine Kinase Inhibitors.

The life expectancy of patients with chronic myeloid leukemia (CML) approaches that of the age-matched population and quality of life (QOL) issues are becoming increasingly important. To describe patients' characteristics and assess QOL, we delivered a 30-item core questionnaire, a 24-item CML-specific questionnaire, both from the European Organization for Research and Treatment of Cancer (EORTC), and additional health-related items to 350 patients. Among 193 patients who completed the questionnaires, 139 received either imatinib (n = 70, 33%), dasatinib (n = 45, 23%) or nilotinib (n = 24, 12%). Patients' median age was 58 (range: 23 to 89) years and 86 (63%) were males. Stratifying patients by treatment, we recognized two distinct populations. In comparison to patients on dasatinib and nilotinib, patients on imatinib were two decades older, had a longer duration of disease and current treatment, experienced fewer limitations on daily activities (p = 0.02), less fatigue (p = 0.001), lower degree of impaired body image (p = 0.022) and less painful episodes (p = 0.014). Similarly, they had better emotional functioning, were less worried, stressed, depressed or nervous (p = 0.01) and were more satisfied with their treatment (p = 0.018). Not only does age associate with current treatments, but it also predicts how patients perceive QOL. Young patients express impaired QOL compared with elderly patients.

Epidural/spinal anesthesia during delivery in women with factor XI deficiency, a single center experience.

INTRODUCTION: The safety of neuro-axial anaesthesia (epidural/spinal) at labour of women with partial factor XI (FXI) deficiency is uncertain. Although FXI deficiency is frequent in Ashkenazi Jews, it is not routinely measured before labour. Our institute serves a large Ashkenazi population. We assumed that 10% of them have undiagnosed FXI deficiency. AIM: Assess the incidence, bleeding tendency and coagulation status among Jewish Ashkenazi women with FXI deficiency that underwent neuro-axial anaesthesia at delivery. METHODS: Jewish Ashkenazi women who underwent neuro-axial anaesthesia at labour completed the SSC ISTH bleeding assessment tool (BAT) and had blood drawn for coagulation tests, FXI and thrombin generation after labour. Estimation for 10 years was calculated from the 1-year sample. RESULTS: We recruited 261 women during 12 months. Among them, 39 (15%) had FXI deficiency (<70%) with median FXI levels of 63% (range: 33%-70%). Around 50% of them underwent amniocentesis in the current pregnancy and prior neuro-axial anaesthesia with no bleeding complications. BAT score and thrombin generation did not differ between women regardless of FXI status. aPTT was longer in women with partial FXI deficiency (median - 28.6 sec vs 26.3 sec, P < .001, Table 2), although within the normal range in all women. No bleeding complications after neuro-axial anaesthesia at delivery were reported in our centre in the last decade though, and according to our estimation, at least 2150 women had partial FXI deficiency. CONCLUSIONS: A significant number of Jewish Ashkenazi women with undiagnosed partial FXI deficiency undergo neuro-axial anaesthesia at labour without bleeding complications.

Prothrombin Complex Concentrate before Urgent Surgery in Patients Treated with Rivaroxaban and Apixaban.

INTRODUCTION: Patients treated with direct Xa inhibitors may require urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is common; however, it is based on limited experience in healthy volunteers. OBJECTIVE: To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery and evaluate its efficacy and safety. METHODS: This was a retrospective study in 2 tertiary hospitals. Bleeding was evaluated based on surgical reports, hemoglobin drop, and the use of blood products or additional PCC during 48 h. Safety measures were thrombotic complications and 30-day mortality. RESULTS: Sixty-two patients aged 80.7 ± 9 years, treated with apixaban (39.63%) or rivaroxaban (23.37%), received PCC before an urgent surgery/procedure. Most underwent abdominal operation (61%), orthopedic surgery (13%), or transhepatic cholecystostomy insertion (10%). Bleeding during surgery was reported in 3 patients (5%), no patient required additional PCC, and 16 patients (26%) received packed cells (median: 1 unit, range: 1-5). The 30-day mortality and thrombosis rates were 21% (n = 13) and 3% (n = 2), respectively. The cause of death was related to the primary disease, most commonly sepsis. No patient died due to bleeding/thrombosis. CONCLUSIONS: Our results support the use of PCC to achieve hemostasis in patients treated with Xa inhibitors prior to an urgent surgery.

Real-life Experience With Ponatinib in Chronic Myeloid Leukemia: A Multicenter Observational Study.

BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase. Only 9 patients (26%) harbored the T315I (threonine to isoleucine mutation at position 315) mutation. All patients had received ≥ 1 previous tyrosine kinase inhibitor. The median age in our cohort was 43 years (range, 9-82 years), significantly younger than expected for patients with relapsed or refractory CML and 20 years younger than the median age of patients who participated in the PACE (ponatinib Philadelphia-positive acute lymphoblastic leukemia and CML evaluation) trial. During a median follow-up of 14 months (range, 1-51 months), the overall response rate was 85%. Of 34 patients, 16 (47%) experienced at least a major molecular response. Of the 37 total patients, another 16 patients (43%) discontinued treatment because of disease progression (n = 6), vascular complications (n = 1), severe cytopenia (n = 2), or for other reasons (n = 7). CONCLUSION: In real life, ponatinib is a "niche-drug" reserved for a unique population of exceptionally young patients with CML with or without the T315I mutation. In this highly selected group, very different from the PACE cohort, ponatinib achieved high overall response rates.

High-Intensity Induction Chemotherapy Is Feasible for Elderly Patients with Acute Myeloid Leukemia.

BACKGROUND: The prognosis of elderly patients with acute myeloid leukemia (AML) is poor, and the best treatment is controversial. Since the majority of AML patients are older than 60 years, identification of those who might benefit from intensive treatment is essential. METHODS: Data from electronic charts of consecutive AML patients treated in our center were analyzed. Eligibility criteria included newly diagnosed de novo or secondary AML, an age of 60 years or older, and intensive induction treatment. RESULTS: Sixty-two patients were included in the analysis. Forty-six patients (74%) achieved complete remission (CR) after 1-2 intensive induction courses. Twenty of them received consolidation with conventional chemotherapy, 20 proceeded to allogeneic hematopoietic cell transplantation (allo-HCT), and 6 were ineligible for further treatment. The projected overall survival (OS) at 2 and 3 years was 28 and 23%, respectively. A normal karyotype, CR achievement, and allo-HCT were associated with improved OS, while an Eastern Cooperative Oncology Group performance status of 0-1 was borderline associated. The median survival and disease-free survival at 2 years was 18.7 months and 49%, respectively, for patients who underwent allo-HCT in CR1, compared to 12.8 months and 25%, respectively, for those who did not. CONCLUSION: Based on our data, selected eligible elderly AML patients might benefit from intensive treatment.

Serum albumin level at diagnosis of diffuse large B-cell lymphoma: an important simple prognostic factor.

This study compared the value of several simple laboratory parameters with known prognostic models for predicting survival in patients with diffuse large B-cell lymphoma (DLBCL). The data of 157 adult patients with DLBCL diagnosed at Rabin Medical Center in 2004-2008 and treated with R-CHOP immunochemotherapy were retrospectively reviewed. Main clinical features of the cohort were as follows: mean age 63.0 years, 43% male, 63% stage III/IV disease, 28% ECOG performance status >2, 60% elevated lactate dehydrogenase level. Median duration of follow-up was 6.6 years. The NCCN-International Prognostic Index (IPI) was found to be a more powerful prognosticator than the IPI. Five-year overall survival (OS) was 69.6; 73.6% for patients with intermediate NCCN-IPI and 38.4% for patients with poor NCCN-IPI. On univariate analysis, pretreatment hemoglobin and albumin levels were significantly associated with survival. By albumin level, 5-year OS was 77.6 + 4% in patients with >3.5 g/dl and 53 + 7% in patients with <3.5 g/dl (p < 0.001); 5-year progression-free survival (PFS) was 69.9% and 50.9%, respectively (p = 0.002). By hemoglobin level, 5-year OS was 82.9 + 4.5% in patients with >12 g/dl and 58.8 + 5% in patients with <12 g/dl (p = 0.007); 5-year PFS was 75.5% and 54.1%, respectively (p = 0.008). On multivariate analysis with Cox regression, pretreatment albumin level was a significant independent predictor of OS. Furthermore, 5-year OS of patients with a high NCCN-IPI and albumin < 3.5 g/dl was 29.2% compared with 60% in patients with albumin > 3.5 g/dl (p = 0.022). In conclusion, pretreatment albumin level is a strong prognostic factor for OS in patients with DLBCL and can discriminate high-risk patients for good and poor prognosis. Copyright © 2015 John Wiley & Sons, Ltd.

Has the time for first-line treatment with second generation tyrosine kinase inhibitors in patients with chronic myelogenous leukemia already come? Systematic review and meta-analysis.

Second generation tyrosine kinase inhibitors have recently been introduced as first-line treatment for chronic phase chronic myelogenous leukemia. We aimed to evaluate the efficacy and safety of 2(nd) generation tyrosine kinase inhibitors versus imatinib as first-line treatment for these patients. We carried out a systematic review and meta-analysis of randomized controlled trials comparing 2(nd) generation tyrosine kinase inhibitors to imatinib as first-line treatment in chronic phase chronic myelogenous leukemia patients. Outcomes assessed were: complete cytogenetic response and major molecular response at 12, 18 and 24 months, all-cause mortality and progression to accelerated phase/blastic crisis at 12, 18 and 24 months, and chronic myelogenous leukemia related mortality and toxicity at last follow up. Relative risks were estimated and pooled using a fixed effect model. Our search yielded four trials including 2,120 patients. At 12 months, treatment with 2(nd) generation tyrosine kinase inhibitors significantly improved both complete cytogenetic response and major molecular response (relative risk 1.16, 95% CI: 1.09-1.23, and 1.68, 95% CI: 1.48-1.91, respectively). While major molecular response was improved at all time points, complete cytogenetic response improved at 18 months but not at 24 months. Importantly, rate of progression to accelerated phase/blastic crisis was significantly lower with the newer tyrosine kinase inhibitors throughout all time points. Second generation tyrosine kinase inhibitors improved chronic myelogenous leukemia related mortality without a statistically significant difference in all-cause mortality at 12, 18 and 24 months. We conclude that 2(nd) generation tyrosine kinase inhibitors can be added safely to the first-line treatment armamentarium of chronic phase chronic myelogenous leukemia patients. Although an advantage is suggested by surrogate parameters, longer follow up is necessary to see if this translates into superior overall survival.

Burkitt's lymphoma of the ovary: case report and review of the literature.

Primary Burkitt's lymphoma of the ovary is extremely rare. We report the case of a 39-year-old woman who presented with a 1-month history complaints of night sweats, abdominal pain and dyspnea. Physical examination demonstrated pleural effusions, ascites and an abdominal mass. Imaging showed enlargement of both ovaries extending to the surrounding tissue. Frozen sections on explorative laparotomy suggested granulosa cell tumor of the ovary, and thus extensive debulking was carried out. The final pathological report was compatible with Burkitt's lymphoma. A systematic literature review revealed another 16 cases of ovarian Burkitt's lymphoma. Characteristics predictive for the diagnosis of Burkitt's lymphoma were: younger age, bilateral ovarian involvement, a rapidly progressive course and high LDH levels.

High-dose imatinib for newly diagnosed chronic phase chronic myeloid leukemia patients--systematic review and meta-analysis.

Imatinib at a dose of 400 mg daily is considered frontline treatment in chronic phase chronic myeloid leukemia (CP-CML). We conducted a systematic review and meta-analysis of randomized controlled trials comparing frontline treatment with imatinib 400 mg daily versus higher doses (≥600 mg daily) in patients with CP-CML. The search yielded four trials, randomizing 1,673 patients. At 12 months, high dose compared with standard dose imatinib improved complete cytogenetic response (CCyR) (RR 1.17, 95% CI 1.08-1.26, four trials, I(2) = 33%) as well as major molecular response (MMolR) (RR 1.26, 95% CI 1.12-1.42, four trials, I(2) = 0%). There was no difference in all-cause mortality or disease progression at the end of follow up. Adverse events requiring discontinuation were more common in the high-dose arm (RR 1.98, 95% CI 1.20-3.26, three trials, I(2) = 0%), as were Grade III/IV neutropenia and thrombocytopenia: RR 1.56, 95% CI 1.15-2.12 and RR 1.86, 95% CI 1.28-2.70, respectively. There is currently insufficient evidence to support the routine use of higher doses of imatinib as frontline treatment for CP-CML. Extended follow up is needed to evaluate if the superior CCyR and MMolR with higher doses of imatinib will translate to long-term clinical benefit.

The use of myeloid colony-stimulating factors in hematologic malignancies: the role of systematic reviews and meta-analyses.

Myeloid colony-stimulating factors (M-CSFs), which include granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), regulate the proliferation and differentiation of myeloid cells. Their use has an important role in the treatment of hematologic malignancies. Guidelines for the use of colony stimulating factors have been published by the American Society of Oncology (ASCO) in 1996 and have been updated several times, most recently in 2006. Meta-analyses of randomized controlled trials are regarded as the highest grade of evidence in clinical research and as such, compared to individual studies, they have more power in answering unresolved clinical issues. In this review, our aim is to evaluate the role of M-CSFs in hematologic malignancies based on meta-analyses conducted in the field.

[Oral antibiotics for non-Hodgkin's lymphoma patients with low risk neutropenic fever--a comparative controlled study].

BACKGROUND: Chemotherapy induced neutropenic fever can be safely treated with oral antibiotics. However, guidelines are based on studies that focused on patients with solid tumors. OBJECTIVE: To evaluate the effectiveness and safety of oral antibiotics in non-Hodgkin's lymphoma (NHL) patients with low risk neutropenic fever. METHODS: The files of all NHL patients who were hospitalized due to low risk neutropenic fever were reviewed. All patients who were hospitalized in our department were treated with oral amoxicillin - clavulanic acid and ciprofloxacin. Patients who were hospitalized in the other departments received parenteral antibiotics. The two modalities were compared for the course and outcome of the febrile disease. RESULTS: The files of 48 patients were reviewed. Most patients had intermediate grade NHL, stages III-IV. Thirty-three patients with 44 episodes of neutropenic fever were treated parenterally, while 15 patients with 19 episodes received oral antibiotics. The two policies had equally successful outcomes (59% in the parenteral group and 74% in the oral group, p=0.270). There was no difference in the rate of mortality, serious complications, secondary infections, no response to initial antibiotic regimen, and antibiotic regimen intolerance. CONCLUSION: The study confirms that oral ciprofloxacin and amoxicillin - clavulanate is a valuable alternative to the parenteral treatment combination in the management of NHL patients with chemotherapy-induced low risk febrile neutropenia.

Glucose control in acutely ill patients: a survey of Israeli internal medicine departments.

BACKGROUND: Tight glucose control has been shown to improve the outcome of patients with severe acute illnesses who are hospitalized in intensive care units and on intravenous insulin-based regimens. OBJECTIVES: To clarify the attitudes of internists towards tight control of glucose levels in acutely ill patients hospitalized in general medical wards. METHODS: A questionnaire on intensive glucose control in acutely ill patients hospitalized in medical wards was mailed to each of the 100 heads of internal medicine departments in Israel. RESULTS: Fifty physicians responded. Of these, 80% considered tight glucose control to be a major treatment target, but only two-thirds had defined it as a goal in their ward. Furthermore, only about half had a defined protocol for such an intervention. Most physicians considered patients with acute coronary syndrome, stroke and infectious diseases as candidates for a tight glucose control protocol. The most frequently used modalities were multiple blood glucose measurements and repeated injections of short-acting subcutaneous insulin. The main reasons given for not having a defined protocol were lack of guidelines, no evidence of a clear benefit during hospitalization on a medical ward, and a shortage of adequately trained staff. CONCLUSIONS: Inconsistencies in physicians' attitudes and in treatment protocols regarding tight control of glucose levels in acutely ill patients hospitalized on a medical ward need to be addressed. Evaluation of the feasibility, effectiveness and side effects of a defined protocol is needed before any regimen can be approved by the heads of the internal medicine departments.