Comparison of conditioning regimen toxicities among autologous stem cell transplantation eligible multiple myeloma patients: High-dose melphalan versus high-dose melphalan and bortezomib.

Background Autologous hematopoietic stem cell transplantation (AHSCT) remains the standard of care for younger patients with multiple myeloma (MM). Currently, high-dose melphalan (HDM) is recommended as conditioning regimen before AHSCT. Preclinical data suggest that combining bortezomib and melphalan has synergistic effect against multiple myeloma cells. Bortezomib and HDM (Bor-HDM) combination as conditioning regimen has been investigated by many other investigators. Objective In this retrospective study, we aimed to compare transplant-related toxicities and hematologic recovery of HDM and Bor-HDM conditioning regimens. Method We retrospectively evaluated hematologic recovery and toxicity profile in patients with MM who received AHSCT with either HDM ( n = 114) or Bor-HDM ( n = 53) conditioning regimen. Results Nonhematologic toxicities were comparable between HDM and Bor-HDM conditioning regimen, except mucositis and diarrhea being more frequent in the Bor-HDM group. Neutrophil and platelet engraftment time and duration of hospital stay were significantly shorter for HDM regimen. Conclusions In this retrospective analysis, we observed engraftment kinetics and duration of hospitalization were significantly worse in Bor-HDM conditioning regimen with manageable toxicities. Randomized studies are needed to further compare Bor- HDM regimen to HDM in terms of response rates, toxicities, and transplant-related mortality.

Factors associated with cytomegalovirus reactivation following allogeneic hematopoietic stem cell transplantation: human leukocyte antigens might be among the risk factors.

OBJECTIVE: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. Current practice includes prophylactic and preemptive treatment modalities, which have risks, side effects, and costs of their own. There is no established risk scoring system that applies to all patients. We aimed to investigate the risk factors for CMV reactivation in AHSCT recipients. MATERIALS AND METHODS: We retrospectively analyzed the risk factors for CMV reactivation in 185 consequent AHSCT recipients transplanted between September 2003 and December 2009 at the Stem Cell Transplantation Unit of Gazi University. Besides the standard transplant-related parameters, HLA antigens were also included among the variables analyzed. RESULTS: Despite the very high rate of donor (94.6%) and recipient (100%) seropositivity, which are the so-called major risk factors in previous reports, our reactivation rate was much lower, with a frequency of 24.9%. The underlying disease, sex, conditioning regimen, and presence of antithymocyte globulin or fludarabine in the conditioning regimen had no impact on reactivation rate. CMV reactivation was significantly more frequent in recipients with graft-versus-host disease (GVHD) compared to those without GVHD (p<0.0001). CMV reactivation was significantly more frequent (p<0.05) in patients with HLA-B14, HLA-DRB1*01, and HLA-DRB1*13 antigens and less frequent in recipients with HLA-A11 and HLA-DRB1*04 antigens (p<0.05). CONCLUSION: Universal risk factors/scores that apply to all transplant recipients are required for tailored prophylaxis and/or treatment strategies for CMV reactivation. Uncovering the role of genetic factors, including HLA antigens, as possible risk factors might lead the way to risk-adaptive strategies for adoptive cellular therapy and/or vaccination.

Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: Acute kidney injury is a relatively frequent complication of allogenic hematopoietic stem cell transplant, resulting in increased risk of morbidity and mortality. Early diagnosis and management of acute kidney injury is of great importance for prevention of poor outcomes in these transplant recipients. MATERIALS AND METHODS: Fifty consecutive patients, hospitalized for allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation Unit of Gazi University Faculty of Medicine, were included in this prospective study. Serial measurements of serum creatinine and creatinine clearance were obtained before administration of conditioning regimen and at 0, 7, 14, 21, and 28 days after start of conditioning. Blood and urine samples were also obtained for the measurement of serum cystatin C and urine neutrophil gelatinase-associated lipocalin levels before conditioning and 24 hours before each serum creatinine measurement. RESULTS: During the median 25 days of follow-up, acute kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2, and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury Network classification. There were significant positive correlations between serum cystatin C levels and serum creatinine levels and negative correlations with creatinine clearance levels at each time point (P < .001), whereas no statistically significant associations were observed with urinary neutrophil gelatinase-associated lipocalin levels. Both univariate and multivariate Cox regression models showed a statistically significant association between serum cystatin C levels and development of acute kidney injury, whereas urine neutrophil gelatinase-associated lipocalin levels did not show any significant associations. CONCLUSIONS: Serum cystatin C levels might be a useful marker for early detection of acute kidney injury in adult allogenic hematopoietic stem cell transplant recipients. Close monitoring of kidney function by sensitive biomarkers might provide early recognition and timely management of acute kidney injury in high-risk patient populations.

Recessive congenital methemoglobinemia in immediate generations.

We report herein on our observation of recessive congenital methemoglobinemia (type I), an autosomal recessive disorder, in immediate generations (in a mother and her daughter). Molecular analysis revealed a mechanism of inheritance not reported previously, despite the high probability of occurrence in autosomal recessive disorders. This report is also the first publication describing an extremely rare mutation (Arg50Gln) causing this disorder in the Turkish population.

Is It Possible to Predict Pulmonary Complications and Mortality in Hematopoietic Stem Cell Transplantation Recipients from Pre-Transplantation Exhaled Nitric Oxide Levels?

OBJECTIVE: Chemo/radiotherapy-induced free oxygen radicals and reactive oxygen derivatives contribute to the development of early and late transplantation-related pulmonary and extra-pulmonary complications in hematopoietic stem cell transplantation (HSCT) recipients. It has been proposed that an increase in fractional exhaled nitric oxide (FeNO) level indicates oxidative stress and inflammation in the airways. The aim of this prospective study is to evaluate the pre-transplantation FeNO levels in HSCT patients and to search for its role in predicting post-transplantation pulmonary complications and mortality. MATERIALS AND METHODS: HSCT patients were included in the study prospectively between October 2009 and July 2011. Pre-transplantation FeNO levels were measured with a NIOX MINO® device prior to conditioning regimens. All patients were monitored prospectively for post-transplantation pulmonary complications with medical history, physical examination, chest X-ray, and pulmonary function tests. RESULTS: A total of 56 patients (33 autologous, 23 allogeneic) with mean age of 45±13 years were included in the study, among whom 40 (71%) were male. Pre-transplantation FeNO level of the whole study group was found to be 24±13 (mean ± standard deviation) parts per billion (ppb). The FeNO level in allogeneic HSCT recipients was 19±6 ppb while it was 27±15 ppb in autologous HSCT recipients (p=0.042). No significant correlation was found between the pre-transplantation chemotherapy and radiotherapy protocols and baseline FeNO levels (p>0.05). Post-transplantation pulmonary toxicity was identified in 12 (21%) patients and no significant relationship was found between baseline FeNO levels and pulmonary toxicity. The survival rate of the whole study group for 1 year after transplantation was 70%. No significant relationship was identified between baseline FeNO values and survival (FeNO 19±7 ppb in patients who died and 26±15 ppb in the survivors; p=0.114). CONCLUSION: Pre-transplantation FeNO measurement does not seem to have a role in predicting post-transplantation pulmonary complications and mortality.

The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks.

Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results. A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion. This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS.

A proven case of cutaneous rhizopus infection presenting with severe limb pain very soon after induction treatment in a patient with acute lymphoblastic leukemia.

Objective and Importance. Invasive mucormycosis may complicate the course of patients with hematologic malignancies and has a very high mortality rate. Early diagnosis and aggressive approach combined with surgical and medical treatment have paramount importance for cure. Clinical Presentation. We report here a case of a patient with acute lymphoblastic leukemia presenting with a subcutaneous mass lesion which was sampled by an ultrasound guided needle biopsy. The pathology showed microorganisms with aseptate hyphae with wide, irregular walls and more or less branching with highly vertical angles which suggested a mold infection. The specimen was also cultured where Rhizopus spp. grew. Conclusion. Posaconazole 200 mg QID was commenced. She recovered from neutropenia and pain on day 20 of treatment. After 4 courses of hyper-CVAD chemotherapy, the remaining soft tissue mass was removed surgically and she underwent allogeneic HSCT from a full matched sibling donor under secondary prophylaxis.

Prognostic factors in critically ill cancer patients admitted to the intensive care unit.

OBJECTIVE: The objective of this study is to identify factors predicting intensive care unit (ICU) mortality in cancer patients admitted to a medical ICU. PATIENTS AND METHODS: We conducted a retrospective study in 162 consecutive cancer patients admitted to the medical ICU of a 1000-bed university hospital between January 2009 and June 2012. Medical history, physical and laboratory findings on admission, and therapeutic interventions during ICU stay were recorded. The study end point was ICU mortality. Logistic regression analysis was performed to identify independent risk factors for ICU mortality. RESULTS: The study cohort consisted of 104 (64.2%) patients with solid tumors and 58 patients (35.8%) with hematological malignancies. The major causes of ICU admission were sepsis/septic shock (66.7%) and respiratory failure (63.6%), respectively. Overall ICU mortality rate was 55 % (n=89). The ICU mortality rates were similar in patients with hematological malignancies and solid tumors (57% vs 53.8%; P=.744). Four variables were independent predictors for ICU mortality in cancer patients: the remission status of the underlying cancer on ICU admission (odds ratio [OR], 0.113; 95% confidence interval [CI], 0.027-0.48; P=.003), Acute Physiology and Chronic Health Evaluation II score (OR, 1.12; 95% CI, 1.032-1.215; P=.007), sepsis/septic shock during ICU stay (OR, 8.94; 95% CI, 2.28-35; P=.002), and vasopressor requirement (OR 16.84; 95% CI, 3.98-71.24; P=.0001). Although Acute Physiology and Chronic Health Evaluation II score (OR, 1.30; 95% CI, 1.054-1.61; P=.014), admission through emergency service (OR, 0.005; 95% CI, 0.00-0.69; P=.035), and vasopressor requirement during ICU stay (OR, 140.64; 95% CI, 3.59-5505.5; P=.008) were independent predictors for ICU mortality in patients with hematological malignancies, Sequential Organ Failure Assessment score (OR, 1.83; 95% CI, 1.29-2.6; P=.001), lactate dehydrogenase level on admission (OR, 1.002; 95% CI, 1-1.005; P=.028), sepsis/septic shock during ICU stay (OR, 138.4; 95% CI, 12.54-1528.4; P=.0001), and complete or partial remission of the underlying cancer (OR, 0.026; 95% CI, 0.002-0.3; P=.004) were the independent risk factors in patients with solid tumors. CONCLUSION: Intensive care unit mortality rate was 55% in our cancer patients, which suggests that patients with cancer can benefit from ICU admission. We also found that ICU mortality rates of patients with hematological malignancies and solid tumors were similar.

Acinetobacter baumannii infection in patients with hematologic malignancies in intensive care unit: risk factors and impact on mortality.

PURPOSE: We investigated the characteristics of Acinetobacter baumannii infection in critically ill patients with hematologic malignancies. MATERIALS AND METHODS: The prospectively collected data of patients with hematologic malignancies admitted to a medical intensive care unit of a university hospital from 2007 through 2010 were reviewed retrospectively. RESULTS: One hundred twenty-eight patients were included in the study, among whom 35 (27%) developed 39 A baumannii infections. Pneumonia was the most common infection site of A baumannii. Presence of neutropenia, underlying hematologic malignancy, and the disease status did not affect the acquisition of the infection. Advancing age, prior exposure to aminoglycosides, central venous catheterization, and presence of nasogastric tube were the independent risk factors for the development of A baumannii infections. The mortality rate was higher in patients with A baumannii infections compared with the ones without (P = .009). However, in multivariate analysis, low Glasgow coma scale, prior immunosuppressive treatment, neutropenia, invasive mechanical ventilation, and severe sepsis were independently associated with mortality, whereas presence of A baumannii infection was not. CONCLUSIONS: Despite the high mortality rate in critically ill patients with hematologic malignancies, presence of A baumannii infection was not an independent risk factor for mortality.