Nuhad Haddad

Eradication of carbapenem-resistant Enterobacteriaceae gastrointestinal colonization with nonabsorbable oral antibiotic treatment: A prospective controlled trial

BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In attempt to eradicate CRE colonization, we conducted a semirandomized, prospective, controlled trial using oral nonabsorbable antibiotics. METHODS Consecutive hospitalized CRE carriers were studied. Patients whose rectal isolates were gentamicin sensitive but colistin resistant were treated with gentamicin. Patients whose isolates were colistin sensitive but gentamicin resistant were treated with colistin. Patients whose isolates were sensitive to both drugs were randomized to 3 groups of oral antibiotic treatment: gentamicin, colistin, or both. Patients whose isolates were resistant to both drugs, and those who did not consent, were followed for spontaneous eradication. RESULTS One hundred fifty-two patients were included; 102 were followed for spontaneous eradication for a median duration of 140 days (controls), and 50 received 1 of the 3 drug regimens: gentamicin, 26; colistin, 16; both drugs, 8, followed for a median duration of 33 days. Eradication rates in the 3 treatment groups were 42%, 50%, and 37.5%, respectively, each significantly higher than the 7% spontaneous eradication rate in the control group (P < .001, P < .001, and P = .004, respectively) with no difference between the regimens. No significant adverse effects were observed. CONCLUSION Oral antibiotic treatment with nonabsorbable drugs to which CRE is susceptible appears to be an effective and safe for eradication of CRE colonization and, thereby, may reduce patient-to-patient transmission and incidence of clinical infection with this difficult-to-treat organism.

Ascites and Pleural Effusion Secondary to Extramedullary Hematopoiesis

Extramedullary hematopoiesis in the pleura and peritoneum is rare. It is usually asymptomatic and generally is diagnosed on post mortem examination. Herein we describe a 33-year-old woman with long-standing myelofibrosis who presented with symptomatic ascites and pleural effusion. After complete evaluation, these were found to have been caused by extramedullary hematopoietic implants to the pleura and peritoneum. The pleural effusion responded to low-dose radiotherapy.

Expression and role in growth regulation of tumour necrosis factor receptors p55 and p75 in acute myeloblastic leukaemia cells

Tumour necrosis factor (TNF)‐α exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin‐3 (IL‐3) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF); (2) inhibition of granulocyte‐CSF (G‐CSF) and stem cell factor (SCF)‐induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF‐Rs), TNF‐Rp55 and TNF‐Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF‐receptor type. This study investigates the roles of these two receptors in TNF‐α‐driven growth regulation of AML blasts in vitro. Using a receptor‐specific antibody, it is shown that both receptor types participate in TNF‐α‐mediated stimulation of GM‐CSF/IL‐3‐induced proliferation and in TNF‐α‐induced autocrine growth. In contrast, the TNF‐α‐triggered growth inhibition (antiproliferation) and the potent suppression of G‐CSF‐ and SCF‐induced proliferation exclusively result from activation of TNF‐Rp55. Taken together, these results suggest that the proliferative effects of TNF‐α on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF‐α‐signalled growth inhibition is exclusively transduced via TNF‐Rp55.

Effects of soluble interleukin‐1 receptor and tumor‐necrosis factor receptor, respectively, on the IL‐1‐ and TNF‐α‐induced DNA synthesis of acute myeloblastic leukemia blasts in vitro

Abstract: This study demonstrates that soluble interleukin‐1 receptor and tumor necrosis factor receptor modulate their corresponding cytokine‐induced DNA synthesis of acute myeloblastic leukemia (AML) blasts in a dose‐dependent, bimodal fashion; at lower concentrations they enhanced, while at high concentrations they inhibited, the cytokine‐mediated effects. Furthermore, the concentrations of endogenously produced IL‐1β and TNF‐a were found to be significantly (p<0.01) higher in supernatants of AML cells cultured in the presence of corresponding soluble receptors compared to their levels in supernatants of cells growing in the absence of these molecules. Our data might suggest that the attenuation of the spontaneous decay of IL‐1β as well as TNF‐a activities by soluble receptors may account for their ability to augment some of their effects.

Allogeneic stem cell transplantation for patients with chronic myeloid leukemia: risk stratified approach with a long-term follow-up.

The use of allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) was almost abandoned in recent years for very effective targeted therapy with tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including SCT. 38 consecutive CML patients were treated (most in preimatinib era) with allogeneic SCT, using partial T cell depletion (TCD) and preemptive donor lymphocyte infusion (DLI), without post‐transplant graft‐versus‐host disease (GvHD) prophylaxis. Conditioning included busulfan, cyclophosphamide, antithymocytic globulin, and fludarabine followed by donor stem cell transfusion. With a median follow up of 90.5 months (1–134), 32 patients are alive. 97% engrafted. 5‐year leukemia free survival (LFS) and overall survival (OS) were 78.95% and 84.2%, respectively. All patients are in major molecular remission and 78% in complete molecular remission. Transplant‐related mortality (TRM) was 13%. Twenty‐four patients received DLI for residual disease. Acute GvHD, mostly Grades I‐II, occurred in 18% of patients post‐transplant and in 24% of patients receiving DLI. In conclusion, the risk‐adapted approach using only partial TCD and preemptive escalated dose of DLI precluded the need for immunosuppressive medications and reduced the risk of significant GvHD without compromising engraftment and long‐term disease control. Am. J. Hematol. 2012.

Respective effects of soluble interleukin‐1 receptor and tumour necrosis factor receptor on IL‐1 and TNF‐α‐induced DNA synthesis of common acute lymphoblastic leukaemia blasts in vitro

This study investigates the capacity of human recombinant interleukin‐1α (IL‐1α), IL‐1β and tumour necrosis factor‐α (TNF‐α) to induce DNA synthesis of highly purified blasts from nine adult common acute lymphoblastic leukaemias (cALL) in 7 d liquid culture.

Postremission therapy with two different dose regimens of cytarabine in adults with acute myelogenous leukemia

Sixty-seven out of 105 (64%) adults with de novo acute myelogenous leukemia (AML), achieving complete remission after induction chemotherapy, entered two successive postremission treatment protocols. Between 1987 and 1989, 35 patients received an intermediate dose of cytarabine (IDAC) along with other drugs. Between 1990 and 1993, 32 patients received high dose cytarabine (HIDAC) with similar other drugs. Patients treated with IDAC had a median survival of 13.8 months (95% CI 11.2-23.1 months) and a 2 year survival of 34.3 +/- 8.0%. Patients receiving HIDAC had a median survival of 35.5 months (95% CI, lower limit 29.8 months) and a 2 year survival of 71.6 +/- 9.4% (P < 0.002). The 2 year actuarial leukemia-free survival (LFS) was 17.8 +/- 6.6% in the IDAC group and 67.3 +/- 10.0% months in the HIDAC group (P = 0.004). The HIDAC group had a significant 2 year survival advantage over the IDAC group only in patients younger than 45 years. The 2 year survival in the first group was 83.3 +/- 10.8% versus 23.5 +/- 10.3% in the IDAC group (P = 0.0001). In patients older than 45 years, no significant differences in 2 year survival was noticed (52.9 +/- 15.78 versus 44.4 +/- 11.7, P = 0.8). Censoring the 21 patients who underwent bone marrow transplantation (BMT) at BMT did not change significantly the survival analysis of the patients in each group. This study is consistent with previous reports favoring HIDAC intensification in the postremission treatment of young patients with AML.

Alloimmune platelet transfusion refractoriness circumvented by allogeneic stem cell transplantation

BACKGROUND: Administration of intensive chemotherapy used in the management of malignancies is accompanied with marrow suppression. Patients undergoing such treatments and especially those with acute leukemia need prolonged blood component support and are at risk for platelet (PLT) refractoriness. Irradiated and filtered blood, although effective, does not eliminate the risk for refractoriness and consequent fatal hemorrhage.

Taking a wider view on fetal/neonatal alloimmune thrombocytopenia

In fetal/neonatal alloimmune thrombocytopenia (FNAIT), platelets are destroyed by maternal antibodies directed against fetal/neonate antigens. Thrombocytopenia can be severe and lead to intracranial hemorrhage (ICH) in about 10% of cases. Although three types of antigen groups, presented on platelets [ABO blood group antigens, human leukocyte antigens (HLA) and human platelet antigens (HPA)] are known to be implicated in immune platelet destruction, antibodies against HPA are most commonly involved in FNAIT and hence are the target of extensive research. Awareness of FNAIT by physicians as well as the availability of the most sensitive diagnostic methods capable of detecting a wide range of antibodies are crucial for the diagnosis of FNAIT and the prevention of severe thrombocytopenia and its bleeding risks in subsequent pregnancies.