Effects of ABO incompatibility in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: The impact of ABO mismatch on outcomes following allo-HSCT remains controversial. In this study, our aim is to define the effect of ABO mismatch on post-transplant outcomes, engraftment kinetics and complications in a large cohort. PATIENTS AND METHODS: We retrospectively identified 1000 patients who underwent allo-HSCT from either bone marrow or peripheral blood stem cells at our center between 1988 and 2016. P<0.05 was considered statistically significant. RESULTS: Five hundred and ninety (59%) patient-donor pairs were ABO matched, 164 (16.4%) were ABO major mismatched (MM), 191 (19.1%) were ABO minor MM, and 55 (5.5%) were ABO bi-directionally MM. ABO matched pairs were more common in transplants from related donors (P<0.001) and using bone marrow as a stem cell source (P<0.001). In minor ABO MM transplantations, mild delayed hemolytic reaction occurred more frequently compared to major and bidirectional ABO MM transplantations (47% vs 35% and 18%, P<0.001). Neutrophil engraftment was slightly delayed in ABO MM patient-donor pairs when compared ABO matched donor pairs according to median engraftment time in all group (167/410, 41% vs 204/590, 35%, P=0.046). Pure red cell aplasia was diagnosed in 6 patients (1%). Higher risk of death was shown in ABO MM transplants compared to ABO matched transplants in overall survival (OS) analysis (HR:1.201, 95% CI:1.004-1.437, P=0.045). The non-relapse mortality (P=0.546) and cumulative incidences of acute graft versus host disease (aGVHD) and chronic (c) GVHD were comparable between ABO MM and ABO matched patient-donor pairs (for aGVHD, P=0.235; for cGVHD, P=0.137). CONCLUSION: ABO MM transplants were associated with decreased OS and slightly delayed neutrophil engraftment. NRM and the risk of GVHD were not related to ABO incompatibility.

Extracorporeal photochemotherapy in mycosis fungoides.

OBJECTIVES: Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF. METHODS: We retrospectively evaluated 50 MF patients who received ECP for clinical activity, toxicity, and response and outcome rates, and we compared these with combination therapies. RESULTS: The overall response rate (ORR) was 42% (21/50), while the median time to response was 11months (range, 3-48months). Ten of the responders (48%) had 3 or more treatment lines prior to ECP. Eight patients (16%) had adverse events related to ECP. The overall survival (OS) of 50 patients was 72months (range, 3-211). There was no statistically significant difference in the OS in early-stage vs late-stage patients (77 vs 69months, P=0.077). The stage 3 and 4 patients received an average of 31 cycles compared to 55 cycles in stage 1 and 2 patients (P=0.006). The increased extent of ECP was not correlated with the response. Combined treatment with ECP significantly improved the OS (84months vs 62months, P=0.005). DISCUSSION: A low frequency of side effects and improved OS observed in combination therapy makes ECP a favorable option for treating MF.

A prospective registration study to determine feasibility of hematopoietic SCT in adults with acute leukemia: planning, expectations and reality.

For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR=0.82; P=0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia.

Periodontal status and post-transplantation complications following intensive periodontal treatment in patients underwent allogenic hematopoietic stem cell transplantation conditioned with myeloablative regimen.

OBJECTIVES: Evaluation of the periodontal status is necessary prior to management with high-dose chemotherapy before hematopoietic stem cell therapy (HSCT). During medical therapy, pre-existing periodontal conditions may exacerbate and cause local and systemic complications. When possible, maximal oral health should be achieved prior to engraftment. In this study, we aimed to determine the alterations occurred in the periodontal status of the patients after periodontal treatment and allogenic HSCT and evaluate the effect of intensive periodontal approach on the short-term complications of HSCT. METHODS: The alterations occurred in the periodontal tissues 3-4 weeks after periodontal treatment and after HSCT periods of 3 months for 29 patients treated with full-mouth periodontal treatment completed in 24 h in addition to eradication of dental foci, and oral hygiene status were evaluated using pocket depth measurements, presence of bleeding on probing and plaque and gingival indices. The incidence and severity of acute graft-versus-host disease (GVHD) and oral mucositis (OM) were recorded. Duration of engraftment period and the episode of febrile neutropenia were also evaluated. RESULTS: There were significant improvements in periodontal status after periodontal treatment (P<0.001). There were 14 (48.3%) patients without acute GVHD and 17 (58.6%) patients with no sign of OM. The majority of OM was at grade II level. There was a negative relation that exists between the percentage of BOP (+) sites and presence of OM (r=-0.518, P<0.05). CONCLUSIONS: Together with a significant reduction in gingival inflammation and maintenance of the improvement in periodontal health, remarkable decrease in the incidence and severity of OM were observed.

Donor lymphocyte infusions for the treatment of chronic myeloid leukemia relapse following peripheral blood or bone marrow stem cell transplantation.

Peripheral blood used as a source of stem cells for transplantation (PBSCT) is known to exert stronger immune-mediated effects compared with BM (BMT). We decided to retrospectively analyze the impact of stem cell source on the OS of CML patients who relapsed after either matched related donor PBSCT (N=168) or BMT (N=216) and were treated with donor lymphocyte infusions (DLI). Univariate analysis revealed a lower probability of OS after DLI in patients relapsing after PBSCT vs BMT (66% vs 79% at 5 years, P=0.013). However, a multivariate Cox analysis did not reveal any significant impact of PBSCT as a risk factor for decreased OS for patients transplanted in first chronic phase (CP1; hazard ratio (HR) 1.036, 95% confidence interval (CI) 0.619-1.734). A statistical interaction term suggested that the impact of stem cell source on OS after DLI was different for those transplanted in advanced phases (negative impact of previous PBSCT-HR 2.176, 95% CI 0.930-5.091). In summary, the stem cell source does not affect the OS of CML patients who underwent PBSCT in CP1, relapsed and were treated with DLI. However, when the patients were transplanted in advanced phases, previous PBSCT seems to negatively affect OS after DLI compared with BMT.

Mobilization of PBSCs with chemotherapy and recombinant human G-CSF: a randomized evaluation of early vs late administration of recombinant human G-CSF.

The optimal timing for recombinant human (rh)G-CSF administration after chemotherapy for PBSC mobilization has not yet been determined. In this study, we compared two different time schedules of rhG-CSF; 4th (early) vs 7th day (late), in 48 consecutive patients with multiple myeloma and lymphoma undergoing PBSC mobilization with CE (CY 4 g/m(2) on day 1 and etoposide 200 mg/m(2) on days 1-3). The rhG-CSF dose was 10 microg/kg/day for all patients. Both groups were comparable in terms of sex, age and number of previously given different chemotherapy regimens. Duration of neutropenia, CD34(+) cell count on the first day of apheresis and numbers of aphereses were not statistically different between the two arms. However, the number of doses of rhG-CSF up to the first cycle of apheresis procedures was significantly lower in the late group than in the early group (P=0.005). The median number of total CD34(+) cells collected was 10.54 x 10(6)/kg (range 0.11-37.27) in the early group and 10.81 x 10(6)/kg (range 0.17-49.83) in the late group of rhG-CSF (P=0.781). We conclude that PBSC mobilization after late use of rhG-CSF is an effective approach and therefore, in routine clinical practice, late rhG-CSF may be used for PBSC collections after chemotherapy-based mobilization regimens in this cost-conscious era.

Turkish Transplant Registry: a comparative analysis of national activity with the EBMT European Activity Survey.

SCT is a curative approach using chemo-, radio- and immunotherapy for malignant and non-malignant hematological disorders. The European Group for Blood and Marrow Transplantation (EBMT) has been collecting yearly data on a survey basis since 1990. The variables within the survey are limited to detailed indications, number of patients, transplant type, stem cell source, type of conditioning regimen and donor type. The transplant rates in certain indications, patterns of stem cell source selection and donor availability and alternative donor use were analyzed in detail. The Turkish transplant registry data within EBMT-European Activity Survey (EBMT-EAS) were delivered by the EBMT Activity Survey Office. We compared the national data with the international EBMT-EAS data pool.

Acoustic monitoring of lung sounds for the detection of one-lung intubation.

INTRODUCTION: Monitoring methods for the early diagnosis of one-lung intubation (OLI) are nonspecific and controversial. In this study, we evaluated a new acoustic monitoring system for the detection of OLI. METHODS: Lung sounds were collected from 24 adult surgical patients scheduled for routine surgical procedures. Four piezoelectric microphones attached to the patients' backs were used to sample lung sounds during induction of anesthesia and endotracheal tube positioning. To achieve OLI, the endotracheal tube was inserted and advanced down the airway so that diminished or no breath sounds were heard on the left side of the chest. The tube was then withdrawn stepwise until equal breath sounds were heard. Fiberoptic bronchoscopy confirmed the tube's final position. Acoustic analyses were preformed by a new algorithm which assumes a Multiple Input Multiple Output system, in which a multidimensional Auto-Regressive model relates the input (lungs) and the output (recorded sounds) and a classifier, based on a Generalized Likelihood Ratio Test, indicates the number of ventilated lungs without reconstructing the original lung sounds from the recorded samples. RESULTS: This algorithm achieved an OLI detection probability of 95.2% with a false alarm probability of 4.8%. CONCLUSION: Higher detection values can be achieved at the price of a higher incidence of false alarms.

Laryngeal mask in prone position: pure exhibitionism or a valid technique.

AIM: The laryngeal mask airway (LMA) is used worldwide during general anesthesia with controlled or spontaneous breathing. Normally its use is limited to patients undergoing surgery in the supine but not the prone position. METHODS: A prospective study of 50 consecutive ASA 1 and 2 patients who underwent ambulatory surgery in the prone position. In the first 25 patients anesthesia was induced in the supine position on a transport trolley after which the patients were turned face down following tracheal intubation. The next 25 patients were asked to lie comfortably in the prone position before receiving anesthesia. Induction and insertion of LMA were performed when they were already prone. RESULTS: There were neither complications nor airway loss when LMA was used in the prone position. The induction-incision time was 23.6+/-3.6 min (range 21-37) in Group 1 and 7+/-2.44 min (range 5-15) in Group 2 (P<0.0001) and the manpower required for positioning (the number of medical and paramedical personnel required to place the patient prone) was considerable reduced in Group 2 (LMA) compared to Group 1 (1.0 versus 3.12+/-0.6 (range 2-4; P<0.0001). Group 2 showed also, significantly more favorable hemodynamic parameters. CONCLUSION: To start anesthesia with patients already prone shortens the induction-incision time, reduces the manpower involved in the positioning process and causes fewer hemodynamic changes than the standard technique of induction and intubation in the supine position followed by turning the patient facedown.

The impact of regional culture on intensive care end of life decision making: an Israeli perspective from the ETHICUS study.

BACKGROUND: Decisions of patients, families, and health care providers about medical care at the end of life depend on many factors, including the societal culture. A pan-European study was conducted to determine the frequency and types of end of life practices in European intensive care units (ICUs), including those in Israel. Several results of the Israeli subsample were different to those of the overall sample. OBJECTIVE: The objective of this article was to explore these differences and provide a possible explanation based on the impact of culture on end of life decision making. METHOD: All adult patients admitted consecutively to three Israeli ICUs (n = 2778) who died or underwent any limitation of life saving interventions between 1 January 1999 and 30 June 2000 were studied prospectively (n = 363). These patients were compared with a similar sample taken from the larger study (ethics in European intensive care units: ETHICUS) carried out in 37 European ICUs. Patients were followed until discharge, death, or 2 months from the decision to limit therapy. End of life decisions were prospectively organised into one of five mutually exclusive categories: cardiopulmonary resuscitation (CPR), brain death, withholding treatment, withdrawing treatment, and active shortening of the dying process (SDP). The data also included patient characteristics (gender, age, ICU admission diagnosis, chronic disorders, date of hospital admission, date and time of decision to limit therapy, date of hospital discharge, date and time of death in hospital), specific therapies limited, and the method of SDP. RESULTS: The majority of patients (n = 252, 69%) had treatment withheld, none underwent SDP, 62 received CPR (17%), 31 had brain death (9%), and 18 underwent withdrawal of treatment (5%). The primary reason given for limiting treatment was that the patient was unresponsive to therapy (n = 187). End of life discussions were held with 132 families (36%), the vast majority of which revolved around withholding treatment (91% of the discussions) and the remainder concerned withdrawing treatment (n = 11, 9%). There was a statistically significant association (chi2 = 830.93, df = 12, p < 0.0001) between the type of end of life decision and region-that is, the northern region of Europe, the central region, the southern region, and Israel. CONCLUSIONS: Regional culture plays an important part in end of life decision making. Differences relating to end of life decision making exist between regions and these differences can often be attributed to cultural factors. Such cultures not only affect patients and their families but also the health care workers who make and carry out such decisions.

Laryngeal mask airway and the Robinow syndrome.

The Robinow syndrome is an extremely rare congenital syndrome that causes facial malformations, as well as genital, cardiac and skeletal abnormalities. Patients with this syndrome undergo several operations during their life. Because of the facial abnormalities they carry a potential risk for difficult intubation. We describe the case of a boy who underwent several operations with documented difficult intubation. The laryngeal mask airway provided a good solution for airway control and afforded adequate ventilation under both controlled mechanical ventilation and spontaneous breathing.

Insertion of the endotracheal tube, laryngeal mask airway and oesophageal-tracheal Combitube. A 6-month comparative prospective study of acquisition and retention skills by medical students.

OBJECTIVE: To assess the ability of medical students to learn and retain skills of airway manipulation for insertion of the endotracheal tube, the laryngeal mask airway (Laryngeal Mask Company, Henley-on-Thames, UK) and the oesophageal-tracheal Combitube (Kendall-Sheridan Catheter Corp., Argyle, NY, USA). METHODS: A 6-month prospective study was conducted among fifth-year medical students attending a 3-week clerkship in the Division of Anesthesiology and Critical Care Medicine in the Soroka Medical Center. All the students viewed a demonstration of insertion technique for the endotracheal tube, the laryngeal mask airway and the Combitube, followed by formal teaching in a mannikin. At the end of the program, the insertion skills were demonstrated in the mannikin, the success rate on the first attempt was registered and the students were requested to assess (by questionnaire) their ability to execute airway manipulation (phase 1). Six months later, the students were requested to repeat the insertion technique, and a similar re-evaluation applied (phase 2). RESULTS: The success rate, during the first phase, at first attempts was 100% for the laryngeal mask airway and the Combitube, compared to 57.4% for the endotracheal tube (P < 0.02), and 92.6%, 96.2% and 62.9% (P < 0.02) respectively for the second phase of the study. CONCLUSION: Learning and retention skills of medical students, in a mannikin, are more accentuated with the laryngeal mask airway and the Combitube than seen with an endotracheal tube.

Increased risk of bloodstream and urinary infections in intensive care unit (ICU) patients compared with patients fitting ICU admission criteria treated in regular wards.

Critically ill patients, eligible for admission into intensive care units (ICUs), are often hospitalized in other wards due to a lack of ICU beds. Differences in morbidity between patients managed in ICUs and elsewhere are unknown, specifically the morbidity related to hospital-acquired infection. Patients fitting ICU admission criteria were identified by screening five entire hospitals on four separate days. Hospital infections within a 30-day follow-up period were compared in ICU patients and in patients on other wards using Kaplan-Meier curves. Residual differences in the patients' case mix between ICUs and other wards were adjusted for utilizing multivariate Cox models. Of 13415 patients screened, 668 were critically ill. The overall infection rates (per 100 patient-days) were 1.2 for bloodstream infection (BSI) and 1.9 for urinary tract infection (UTI). The adjusted hazard ratios in ICU patients compared with patients on regular wards were 3.1 (P<0.001) for BSI and 2.5 (P<0.001) for UTI. This increased risk persisted even after adjusting for the disparity in the number of cultures sent from ICUs compared with ordinary wards. No interdepartmental differences were found in the rates of pneumonia, surgical wound infections and other infections. Minimizing the differences between characteristics of patients hospitalized in ICUs and in other wards, and controlling for the higher frequency of cultures sent from ICUs did not eliminate the increased risk of BSI and UTI associated with admission into ICUs.

Does supplemental perioperative oxygen administration reduce the incidence of wound infection in elective colorectal surgery?

AIM: An association has been proposed between perioperative administration of 80% oxygen and a lower incidence of wound infection after colorectal surgery. The present study was conducted to assess this hypothesis. METHODS: Thirty-eight patients (ASA classification 1 and 2) undergoing elective colorectal cancer surgery were allocated at random to 2 groups. Group 1 consisted of 19 patients who received an admixture of 80% oxygen and 20% nitrogen during anesthesia through an orotracheal tube and during the 2 first hours in the recovery room through a tight facemask with reservoir. Group 2 consisted of 19 patients who received an admixture of 70% nitrous oxide and 30% oxygen during anesthesia, followed by administration of 30% oxygen delivered by a blender through a tight facemask with reservoir in the same manner than group 1, during the first 2 hours in the recovery room. Wound infection was evaluated daily during hospital stay and after 7 days, 2 weeks, and 1 month. RESULTS: The incidence of wound infection was 12.5% in group 1 and 17.6% in group 2 (p=0.53). CONCLUSIONS: The results of this study showed no reduction in the incidence of wound infection following elective colorectal surgery in patients receiving 80% oxygen during the perioperative period.

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation in patients with lymphoma -- a retrospective evaluation.

The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m2), melphalan (100 mg/m2), and carboplatin (1050-1350 mg/m2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occurred in five of 42 (12%) patients and death due to grade-4 RRT occurred in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.

The anaesthetic management of patients with congenital insensitivity to pain with anhidrosis.

BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA, or hereditary sensory and autonomic neuropathy type IV) is a rare, autosomal recessive disease, related to a mutation in the TrkA gene, characterized by inability to sweat, insensitivity to pain and recurrent episodes of hyperpyrexia. There are two Bedouin tribes in Israel with different mutations of the TrkA gene: one in the southern region and the other in the northern region. The Soroka University Medical Center is the referral centre for the entire southern region of Israel. One in 4500 anaesthesia cases involves a patient with CIPA. METHODS: We reviewed 40 anaesthesia records of 20 patients with CIPA for anaesthetic technique and incidence of side-effects. RESULTS: Sixteen patients developed complications in the immediate perioperative period: mild hypothermia in one patient and cardiovascular events in 15 others with one case of cardiac arrest. These complications were unrelated to the anaesthetic drug administered. There were no events of hyperthermia or postoperative nausea. CONCLUSIONS: Cardiovascular complications following anaesthesia are common in patients with the southern Israel variant of CIPA. Hyperthermia, previously recognized as a major concern in patients with congenital insensitivity to pain with anhydrous, was not seen in our patients. We conclude that cardiovascular involvement is frequently encountered in CIPA patients following anaesthesia and is the major concern in their anaesthetic management.

Retrograde tracheal intubation: beyond fibreoptic endotracheal intubation.

BACKGROUND: Flexible fibreoptic laryngoscopy is the method of choice for coping with difficult tracheal intubations, a leading cause of catastrophic outcomes in anaesthesia. However, this technique is not always available or feasible. Retrograde intubation is a minimally invasive airway management technique with a flat learning curve and a high level of skill retention. METHODS: A retrospective review of the anaesthesia records of 24 patients who underwent retrograde intubation. The success rate and the incidence of complications were recorded. RESULTS: Retrograde tracheal intubation was successful in all 24 patients. In 21 patients it succeeded on the first attempt. In two patients it succeeded when the technique was changed from sliding over a guide wire to a pulling technique. The most common complication was a sore throat in almost 60% of the patients. Two patients had mild subcutaneous emphysema and one had minimal bleeding at the puncture site. CONCLUSIONS: In these patients retrograde tracheal intubation was easy to perform, had a high success rate and a low incidence of complications. It is a reliable alternative when fibreoptic intubation is precluded, fails or is unavailable.