Decreased Rejection and Improved Survival of First and Second Marrow Transplants for Severe Aplastic Anemia (A 26-Year Retrospective Analysis)

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2742-2749
Author(s):  
Anne Stucki ◽  
Wendy Leisenring ◽  
Brenda M. Sandmaier ◽  
Jean Sanders ◽  
Claudio Anasetti ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Graft Rejection ◽  
Marrow Transplant ◽  
Severe Aplastic Anemia ◽  
Probability Of Survival ◽  
Gvhd Prophylaxis ◽  
Group 3 ◽  
Group 2 ◽  
American Society ◽  
Group 1

Between 1970 and 1996, 333 patients with severe aplastic anemia underwent HLA-matched related marrow transplant after conditioning with cyclophosphamide (CY). Thirty-five percent of patients transplanted between 1970 and 1976 (group 1), 12% of those transplanted between 1977 and 1981 (group 2), and 9% of patients transplanted between 1982 and 1997 (group 3) had graft rejection. Graft rejection occurred later among group 3 patients (median, 180 days) than among those in groups 1 and 2 (medians, 28 and 47 days, respectively; P < .001 group 3 v 2). In group 3, 92% of rejecting patients underwent a second transplant, compared with 78% and 77% in groups 1 and 2, respectively. Group 1 patients received various conditioning regimens before second transplant, whereas most patients of groups 2 and 3 received CY combined with antithymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis after second transplant consisted of methotrexate (MTX) for all group 1 and 2 patients, whereas group 3 patients received MTX combined with cyclosporine (CSP). Over the three time periods studied, first graft rejection decreased from 35% to 9%, and the proportion of rejecting patients undergoing second transplants increased from 77% to 92%. The 10-year probability of survival after second transplants increased from 5% to 83%. Multivariate analysis showed MTX/CSP GVHD prophylaxis to be a significant factor accounting for the increase in patient survival after second transplant. © 1998 by The American Society of Hematology.

Decreased Rejection and Improved Survival of First and Second Marrow Transplants for Severe Aplastic Anemia (A 26-Year Retrospective Analysis)

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2742-2749 ◽  
Author(s):  
Anne Stucki ◽  
Wendy Leisenring ◽  
Brenda M. Sandmaier ◽  
Jean Sanders ◽  
Claudio Anasetti ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Graft Rejection ◽  
Marrow Transplant ◽  
Severe Aplastic Anemia ◽  
Probability Of Survival ◽  
Gvhd Prophylaxis ◽  
Group 3 ◽  
Group 2 ◽  
American Society ◽  
Group 1

Abstract Between 1970 and 1996, 333 patients with severe aplastic anemia underwent HLA-matched related marrow transplant after conditioning with cyclophosphamide (CY). Thirty-five percent of patients transplanted between 1970 and 1976 (group 1), 12% of those transplanted between 1977 and 1981 (group 2), and 9% of patients transplanted between 1982 and 1997 (group 3) had graft rejection. Graft rejection occurred later among group 3 patients (median, 180 days) than among those in groups 1 and 2 (medians, 28 and 47 days, respectively; P &lt; .001 group 3 v 2). In group 3, 92% of rejecting patients underwent a second transplant, compared with 78% and 77% in groups 1 and 2, respectively. Group 1 patients received various conditioning regimens before second transplant, whereas most patients of groups 2 and 3 received CY combined with antithymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis after second transplant consisted of methotrexate (MTX) for all group 1 and 2 patients, whereas group 3 patients received MTX combined with cyclosporine (CSP). Over the three time periods studied, first graft rejection decreased from 35% to 9%, and the proportion of rejecting patients undergoing second transplants increased from 77% to 92%. The 10-year probability of survival after second transplants increased from 5% to 83%. Multivariate analysis showed MTX/CSP GVHD prophylaxis to be a significant factor accounting for the increase in patient survival after second transplant. © 1998 by The American Society of Hematology.

Optimal TBI Dose to Improve the Survival in Unrelated Matched Marrow Transplantation for Adult Patients with Severe Aplastic Anemia: Prospective De-Escalation Study of TBI Dose.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2770-2770
Author(s):  
Jong-Wook Lee ◽  
Ki Seong Eom ◽  
Yoon Hee Park ◽  
Yoo Jin Kim ◽  
Seok Lee ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Severe Aplastic Anemia ◽  
Fixed Dose ◽  
Unrelated Donor ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background and Objectives: Patients with severe aplastic anemia (SAA) who do not have suitably HLA-matched related donor generally receive immunosuppressive therapy (IST) as first-line treatment and are considered for transplantation from matched unrelated donor (MUD) if they fail to respond to IST. To determine the optimal total body irradiation (TBI) dose as conditioning regimen in unrelated marrow transplantation for adult SAA patients, we conducted a prospective study to evaluate minimal dose of TBI sufficient to achieve sustained engraftment when it is used in combination with fixed dose of cyclophosphamide (CY). Methods: Between May 1998 and December 2003 twenty-eight patients were enrolled with a median age of 23 years old (20–44). All patients were multiply transfused and had received 1 or 2 course of intensive IST. Conditioning regimen consisted of CY (120mg/kg) plus TBI and they were divided into 3 group according to the fractionated TBI dose: group 1 (1200 cGy, n=5), group 2 (1000 cGy, n=9), and group 3 (800 cGy, n=14). Donor/recipient pairs were matched for HLA-A, -B by serology and -DRB1 by low-resolution DNA typing (n=15) or HLA-A, -B, and -DRB1 by high-resolution typing (n=13). Patients received CsA+MTx (n=4) or FK506+MTx (n=24) as GVHD prophylaxis. Results: All patients except one (group 2) achieved sustained engraftment. The incidence of acute GVHD more than grade II was not significantly different (60% in group 1, 38% in group 2, and 43% in group 3), but chronic GVHD developed more frequently in group 1 and 2 (60% & 80%, respectively) compared to group 3 (15%). Patients who received 800 cGy (group 3) had significantly better survival than those 1000 and 1200 cGy (93% in group 3, 44% in group 2, and 40% in group 1; group 3 vs group 1 and 2, p&lt;0.02). Conclusions: Thus, a TBI dose of 800 cGy in combination with CY (120mg/kg) was sufficient to allow for engraftment in adult patients with SAA who received MUD BMT. Outcome in patients who received 800 cGy of TBI was superior to survival that among patients 1000 and 1200 cGy.

Addition of More Immunosuppressive Drugs As Graft-Versus-Host Disease (GVHD) Prophylaxis Does Not Improve Gvhd Outcomes in Reduced Intensity Allogeneic Hematopoietic Cell Transplantation from Unrelated Donors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5786-5786
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Fiorenza Barraco ◽  
Xavier Thomas ◽  
Marie Balsat ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Immunosuppressive Drugs ◽  
Advisory Committees ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Group 3 ◽  
Group 2 ◽  
Related Mortality ◽  
Group 1

Abstract Background: Reduced-intensity conditioning (RIC) regimens have led to a dramatic reduction of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The concept of RIC is to deliver adequate immunosuppression with manageable graft-versus-host disease (GVHD) and the eventual development of a potent graft-versus-leukemia effect. Nevertheless, GVHD prophylaxis remains a challenging task after allo-HSCT. While the combination of cyclosporine A (CsA) and a short course of methotrexate (Mtx) after transplantation is considered as the gold standard for GVHD prophylaxis after conventional myeloablative allo-HSCT from HLA-identical siblings, there is no consensus on the optimal preventive GVHD prophylaxis after RIC allo-HSCT. On the other hand, recent and ongoing studies are evaluating a promising GVHD prophylaxis strategy using post-transplantation cyclophosphamide (PTCy). The aim of this study is to evaluate the impact of different GVHD prophylaxis used after RIC allo-HSCT in patients receiving peripheral blood stem cells (PBSC) from unrelated donors for hematological malignancies. Patients and methods: We evaluated 127 consecutive patients with hematological malignancies who received RIC allo-HSCT and were followed in our center between January 2008 and January 2016; 74 (58%) were males, median age was 58 years (range: 18-70), 52 (41%) had acute myeloid leukemia, 36 (28%) myelodysplastic syndrome, 12 (10%) myeloproliferative syndrome, 9 (7%) Non-Hodgkin lymphoma, 9 (7%) chronic lymphocytic leukemia, 6 (5%) multiple myeloma and 3 (2%) chronic myeloid leukemia. At transplantation, 65 (51%) patients were in complete response (CR) or chronic phase (CP). RIC regimen consisted on fludarabine, intermediate doses of IV busulfan and anti-thymocyte golbulins (ATG) (Thymoblobulin) in 56 (44%) patients and a sequential FLAMSA regimen in 71 (56%) patients and who also received similar doses of ATG (Thymoglobulin). PBSC donors were 10/10 HLA matched in 81 (64%) patients and 9/10 HLA mismatched in 46 (36%) patients. Patients were divided according to GVHD prophylaxis into 3 groups: group 1 consisted on CsA alone with 23 (18%) patients, group 2 include patients who received either CsA + mycophenolate mofetil (MMF), n= 64 (50%) or CsA + Mtx, n= 20 (16%) or CsA + cyclophosphamide n= 5 (4%), and group 3 included patients receiving CsA + MMF + tacrolimus n= 15 (12%) patients. Results: After transplantation, all patients in group 1 engrafted after a median of 17 (3-25) days, 81/89 (91%) engrafted in group 2 after a median of 17 (5-58) days and 14/15 (94%) engrafted in group 3 after a median of 16 (9-24) days. We did not observe any significant impact of the type of GVHD prophylaxis on the 100-day incidence of grade II to IV acute GVHD, which occurred in 6/15 (40%), 34/81 (42%) and 7/14 (50%) for the groups 1, 2 and 3 respectively (p=0.18). Grade III-IV acute GVHD occurred in 3 (20%), 24 (29%) and 5 (33%) in the three groups respectively (p=0.11). Similarly, cumulative incidence of 1 year chronic GVHD was not different between groups 1, 2 and 3 reaching 46%, 43% and 46% respectively (p=0.6) among them 3/15 (20%), 18 (22%) and 3/14 (21%) patients had an extensive form. After a median follow-up of 22 months for surviving patients, although there was no significant difference between the three groups in terms of non-relapse mortality, we observed more infection-related mortality with 45% and 83% in groups 2 and 3 respectively compared to 47% in group 1. The cumulative incidence of relapse at 2 years was 22%, 31 and 26% for the three groups respectively (p=0.23). Overall survival rates at two years were 43%, 31% and 44 % for groups 1, 2 and 3 respectively (p=0.42). The multivariate analysis taking into account the type of disease, donor HLA matching, disease status at transplantation, type of RIC and the type of prophylaxis, showed that the incidence of acute GVHD was influenced only by the use of FLAMSA regimen from mismatched donors, HR= 2.2 [1.3-3.1], p=0.05 which had also the same impact on the occurrence of chronic GVHD. Conclusion: Despite its limitations and the need for prospective randomized studies, the results of our study suggest that in the RIC allo-HSCT from unrelated donors, the different GVHD prophylaxis associations lead to similar GVHD outcomes. Patients with more immunosuppressive drugs had a higher incidence of infection-related mortality and in which PTCy could be a better option. Disclosures Nicolini: BMS: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees.

The Staircase Phenomenon

2001 ◽  
Vol 95 (2) ◽  
pp. 403-407 ◽  
Author(s):  
Aaron F. Kopman ◽  
Sanjeev Kumar ◽  
Monika M. Klewicka ◽  
George G. Neuman
Keyword(s):  
Mechanical Response ◽  
Additional Information ◽  
Laryngeal Mask Insertion ◽  
Train Of Four ◽  
Group 3 ◽  
Group 2 ◽  
American Society ◽  
Time Required ◽  
Few Data ◽  
Group 1

Background Repeated indirect stimulation enhances the evoked mechanical response of muscle (the staircase phenomenon). There are few data that document the magnitude of this effect in man. Inexpensive acceleromyographic monitors of neuromuscular function are now available. If these units are to be used as scientific tools or clinical monitors, additional information regarding how to achieve proper baseline stabilization and calibration is needed. Methods Anesthesia was induced and maintained with nitrous oxide, propofol, and an opioid. Tracheal intubation or laryngeal mask insertion was accomplished without muscle relaxants. Thirty adult patients classified as American Society of Anesthesiologists physical status I or II were divided into groups of 10. The mechanical response of the thumb to supramaximal ulnar nerve stimulation was recorded continuously with an acceleromyograph. Group 1 had train-of-four stimuli at 15-s intervals for 25 min. Group 2 had single stimuli at 1.0 Hz for 10 min. Group 3 had the same stimuli as group 1 except that a 50-Hz tetanus of 5 seconds' duration immediately preceded instrument calibration. Results In group 1, average twitch height (T1) increased rapidly to 148+/-19% (mean +/- SD) of control at 15 min and then more slowly to reach 158+/-26% of control at 25 min. The train-of-four fade ratio did not vary with the duration of stimulation. In group 2, T1 increased to 172+/-19% of control after 400 stimuli (6.7 min) and 180+/-22% of control at 10 min In group 3, average T1 did not decrease below 97+/-5% or increase above 105+/-15% of control at any time. Conclusions A 5-s, 50-Hz tetanus administered before initial twitch calibration considerably shortens the time required to achieve baseline stability.

Evaluation of Three Different Cyclosporine-Based Graft Versus Host Disease (GVHD) Prophylaxis Regimens Following Nonmyeloablative Hematopoietic Stem Cell Transplantation (NST).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1236-1236 ◽  
Author(s):  
Ramaprasad Srinivasan ◽  
Nancy Geller ◽  
Sakti Chakrabarti ◽  
Igor Espinoza-Delgado ◽  
Teresa Donohue ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Malignant Diseases ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
High Incidence ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Acute GVHD is a major contributor to morbidity and mortality following NST. A high incidence of grades II–IV GVHD occurs when cyclosporine A (CSA) alone is used as prophylaxis. Consequently, we investigated the effect of combining either mycophenolate mofetil (MMF) or methotrexate (MTX) with CSA on the incidence and severity of acute GVHD. Between 11/97 and 07/04, 185 consecutive patients (solid tumors n=116, hematologic malignancies n=48, non-malignant hematologic disorders n=21) underwent nonmyeloablative conditioning with fludarabine (125mg/m2) and cyclophosphamide (120mg/kg), followed by a G-CSF mobilized peripheral blood hematopoietic stem cell transplant from an HLA identical (n=177: 96%) or 5/6 antigen-matched (n=8: 4%) related donor. Twenty-four patients with a history of heavy RBC transfusions or those receiving a 5/6 HLA-matched transplant had anti-thymocyte globulin (40mg/kg/d x 4 days) added to their conditioning regimen. The initial cohort of patients (Group 1, n=66), received CSA alone (dose adjusted to maintain therapeutic serum levels) as GVHD prophylaxis. Due to the high incidence of severe acute GVHD in this group subsequent patients received CSA with either MMF (1 gram po bid; Group 2, n=82) or MTX (5mg/m2 days +1, +3, +6; Group 3, n=37). In all three groups, decisions regarding discontinuation of immunosuppression were based on the degree of donor T cell chimerism, presence of GVHD, and disease status in those with malignant diseases. In the absence of grade II–IV GVHD and disease progression, CSA (+/− MMF) was tapered slowly beginning on day +60. Baseline characteristics of patients in the three groups were compared using the Wilcoxon test for continuous variables and chi-squared tests for discrete variables. The three groups did not differ significantly in terms of age, sex, sex mismatch (female into male) and CD34 cell dose. Median follow-up in groups 1, 2 and 3 was 1901 days, 1248 days and 346 days respectively. The cumulative incidence of grades II–IV GVHD in these three groups was 56% (95% CI 44%–68%), 59% (95% CI, 48%–70%), and 34% (95% CI 18%–50%, p=0.11) respectively. The cumulative incidence of grades III–IV GVHD (30% vs. 34% vs. 16%, p=0.2) and the incidence of chronic GVHD (46% vs. 57% vs. 50%, p=0.49) were also similar in the three groups. Transplant related mortality was 15% (95% CI, 6%–24%) in group 1, 12% (95% CI, 5%–19%) in group 2 and 5% (95% CI, 0%–13%) in group 3 patients (p=0.44). The cumulative incidence of death from acute GVHD was 9% (95% CI, 0%–16%) and 2% (95% CI, 0–5%) respectively in groups 1 and 2, while no deaths from acute GVHD occurred in group 3. Overall survival in the three groups did not differ significantly (log-rank test, p=0.48), with medians 244 days (95% CI 196–402), 486 days (95% CI 306–620) and 438 days, (95% CI 210–662) respectively. The impact of adding MMF or MTX to CSA on disease-specific outcome in patients with malignant diseases was not assessed. Conclusion: There was a trend towards a lower incidence of grades II–IV GVHD in group 3 patients. However, despite the addition of either MMF or MTX to CSA, severe grade III–IV acute GVHD remains a major morbidity complicating NST. Additional strategies aimed at preventing GVHD and optimizing the management of established GVHD are needed to improve outcome following this approach.

Reduced Incidence of Acute Graft Versus Host Disease (GVHD) and Transplant-Related Mortality (TRM) with the Addition of Short-Course Mini-Dose Methotrexate (MTX) to Cyclosporine (CSA) as GVHD Prophylaxis Following Nonmyeloablative Hematopoietic Stem Cell Transplantation (NST).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2990-2990 ◽  
Author(s):  
Ramaprasad Srinivasan ◽  
Haley Hedlin ◽  
Rose Goodwin ◽  
Aleah Smith ◽  
Catalina Ramos ◽  
...  
Keyword(s):  
Lower Incidence ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Dose Methotrexate ◽  
Gvhd Prophylaxis ◽  
High Incidence ◽  
Group 3 ◽  
Group 2 ◽  
Related Mortality ◽  
Group 1

Abstract Acute GVHD is a major cause of morbidity and mortality following NST. A high incidence of aGVHD occurs when CSA alone is used as prophylaxis. We investigated the effect of combining either mycophenolate mofetil (MMF) or an abbreviated course of low dose MTX with CSA on the incidence and severity of aGVHD. Between 11/97 and 07/07, 230 consecutive patients (pts) (solid tumors n=127, hematologic malignancies n=57, non-malignant hematologic disorders n=46) underwent conditioning with fludarabine (125mg/m2) and cyclophosphamide (120mg/kg), followed by a G-CSF mobilized PBSC transplant from an HLA identical (n=222: 96%) or 5/6 HLA-matched (n=8: 4%) related donor. Forty-eight pts with a history of heavy RBC transfusions or those receiving a 5/6 HLA-matched transplant had ATG (40mg/kg/d × 4 days) added to their conditioning. The initial cohort of pts (Group 1, n=66), received CSA alone (dose adjusted to maintain therapeutic serum levels) as GVHD prophylaxis. Due to the high incidence of severe aGVHD in this group, subsequent pts received CSA with either MMF (1 gram po bid; Group 2, n=82) or an abbreviated course of mini-dose MTX (5mg/m2 days +1, +3, +6; Group 3, n=82). In all three groups, decisions regarding discontinuation of CSA and MMF were based on donor T cell chimerism, presence of GVHD, and disease status. With a median follow-up of 2963, 2317 and 894 days in the three consecutive cohorts, a comparison was undertaken using competing risk analysis. The incidence of grades II–IV and III–IV GVHD was significantly higher in pts receiving CSA alone or CSA+MMF compared to those receiving CSA+MTX; the cumulative incidence of grades II–IV GVHD in the three groups was 56%, 59%, and 37% (p=0.05) while grades III–IV GVHD occurred in 30%, 34%, and 15% (p=0.019) respectively. The incidence of chronic GVHD (45% vs. 57% vs. 46%, p=0.27) was similar in the three groups. The lower incidence of aGVHD associated with MTX use was accompanied by a significantly improved TRM in group 3 pts; transplant related mortality was 21% in group 1, 21% in group 2 and 5% in group 3 pts (p=0.019). The impact of adding MMF or MTX to CSA on disease-specific outcome in pts with different malignant diseases could not be assessed due to small sample sizes. Conclusion: The addition of an abbreviated course of mini-dose methotrexate to CSA was associated with a significantly lower incidence of grades II–IV and III–IV aGVHD as well as lower TRM compared with CSA used alone or in combination with MMF in pts undergoing NST. To our knowledge this is the first report demonstrating a benefit of adding mini-dose MTX for GVHD prophylaxis in patients undergoing NST. Group 1 (N=66) Group 2 (N=82) Group 3 (N=82) P value Cumulative Incidence of Grade II–IV aGVHD (95% CI) 56% (44%–68%) 59%(48%–70%) 37%(25%–49%) 0.05 Cumulative Incidence of Grade III–IV aGVHD (95% CI) 30%(19%–41%) 34%(22%–46%) 15%(7%–23%) 0.019 Transplant Related Mortality(95% CI) 21%(11%–31%) 21%(12%–30%) 5%(0%–7%) 0.019 Proportion of Evaluable Pts with Chronic GVHD (%) 24/53 (45%) 43/75(57%) 34/74(46%) 0.274

The Challenge of Diagnosing Fanconi Anemia in Patients with Bone Marrow Failure (BMF): A Study in 82 BMF Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 991-991 ◽  
Author(s):  
Fernando O. Pinto ◽  
Thierry Leblanc ◽  
Gwenaelle Le Roux ◽  
Jerome Larghero ◽  
Bruno Cassinat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Somatic Mosaicism ◽  
Chromosome Breakage ◽  
Clinical Findings ◽  
Group 3 ◽  
Group 2 ◽  
Rule Out ◽  
Group 1

Abstract The Bone Marrow Failure (BMF) syndromes comprise a variety of distinct acquired or inherited clinical entities. Early distinction between syndromes has clear implications in the disease management and outcome. Fanconi anemia (FA), the most frequent cause of inherited BMF, is usually associated with congenital abnormalities, progressive cytopenia, chromosome fragility, and cancer susceptibility. However, due to a high clinical variability and/or the potential emergence of revertant hematopoietic cells (somatic mosaicism), identifying patients with FA or ruling out this diagnosis can be challenging. If undiagnosed, FA patients who initially present with bone marrow failure will die of toxicity after standard-dose conditioning regimens for HSCT. In this study, we evaluated FA diagnosis in patients with BMF but no clear initial evidence of FA, using of a combination of classical and innovative tests in blood and fibroblasts. A cohort of 82 patients with BMF and no strong clinical evidence of FA was analysed (patients with a clear FA diagnosis were not included). Based on the likelihood of an underlying inherited condition associated with the BMF, we classified patients in 3 groups: those likely to have idiopathic aplastic anemia (IAA) [n=38, group 1], those likely to have a constitutional condition other than FA [n=26, group 2], and those likely to have IAA but who had isolated clinical findings which could also be present in FA [n=18, group 3]. Chromosome breakage test and analysis of the FA/BRCA pathway by FANCD2 immunoblot were performed in PBL in all patients [n= 82]. To overcome potential somatic mosaicism, skin primary fibroblasts were analysed [n= 52]. Also, to rule out FA/BRCA downstream groups, we developed a new flow cytometry test based on MMC-sensitivity in fibroblasts. In total, 6 patients with FA were identified: 1/38 in group 1 (aplastic anemia at 10 yo, no positive clinical findings), 2/26 in group 2 (one with MDS at 48 yo with precocious menopause and vocal cord neoplasia at 38 yo; one with hypoplastic MDS at 50 yo), and 3/18 in group 3 (one with short stature and aplastic anemia at 37 yo; one with MDS and borderline physical abnormalities at 26 yo; and one with a single cafe-au-lait spot and aplastic anemia at 10 yo). Chromosomal breakage tests in PBL were sufficient to diagnose 4 of these FA patients (further classified as FA core using FANCD2 immunoblot). Additional fibroblast analyses were necessary to identify 2 more FA patients (both with complete somatic mosaicism) and, importantly, to definitely exclude FA diagnosis in other patients. In conclusion, underdiagnosing FA is rare if careful history and physical exam are done together with chromosome breakage test in PBL. However, in clinical situations where the suspicion of FA persists despite negative breakage tests, then fibroblasts should be tested. Because no cases of FA were found among patients with IAA and negative breakage tests in PBL, we suggest that FA screening can be limited to this technique in this population (group 1). The strategy here presented allowed us to identify a few unexpected FA cases in a cohort of BMF patients, and importantly, to definitely rule out FA in others, with clear clinical impact for patients who undergo HSCT.

scholarly journals COMPARISON OF ESMOLOL, LABETALOL AND LIGNOCAINE FOR ATTENUATION OF SYMPATHOMIMETIC RESPONSES TO LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Dr. Ankit Kumar ◽  
Dr. Arun Kumar Kulshrestha
Keyword(s):  
Blood Pressure ◽  
Endotracheal Intubation ◽  
Stress Responses ◽  
Left Ventricular ◽  
Group Reduction ◽  
Group 3 ◽  
Group 2 ◽  
Artery Disease ◽  
American Society ◽  
Group 1

INTRODUCTION: In some individual’s suffering from hypertension, coronary artery disease, cerebrovascular disease, myocardial infarction and thyrotoxicosis, these hemodynamic stress responses can turn into life-threatening conditions like left ventricular failure, myocardial ischemia, cerebral hemorrhage, and ruptured cerebral aneurysm. Different drugs like lidocaine, vasodilator agents inhibiting sympathoadrenal response, α-and β-adrenergic blockers, and opioids can be administered prior to tracheal intubation to prevent hemodynamic responses. But higher dose of lignocaine may lead to hypotension, bradycardia, and hypoxia in patients. Due to various effect of these drugs on hemodynamic changes in patients this study was carried out to evaluate the effects of IV esmolol, lignocaine, and labetalol for attenuation of hemodynamic response to laryngoscopy and intubation. MATERIAL AND METHODS: A total of 90 consecutive patients were included in the study and were grouped in to, lignocaine group, labetalol and esmolol group containing 30 patients each. Age group 21–65 years of either sex or American Society of Anesthesiologists (ASA) Grade I or II scheduled for various general surgical procedures under endotracheal anesthesia were included in this study. Patients excluded were pregnant and lactating women, morbid obesity, and hypertension. RESULTS: Mean Age in Group 1, group2 and group 3 was 40.38 ± 7.25, 43.8 ± 9.24 and 42.56 ± 8.71 respectively while weight was 62.41 ± 7.32, 63.63 ± 8.11 and 60.74 ± 6.92 respectively. There were 17 male and 13 female in group 1, 19 male and 11 female in group 2 and 16 male and 14 female in group 3. Attenuation of blood pressure was more in labetalol group. Reduction of heart rate in labetalol group was significant. It is seen that Labetalol was more effective at attenuation of diastolic blood pressure among all drugs. Mean arterial pressure was not much reduced lignocaine and esmolol group as compared to labetalol. CONCLUSION: Haemodynamic alterations are usually observed during laryngoscopy and endotracheal intubation. In our study it was found that as labetalol is a safe and effective drug, for attenuation of sympathomimetic response.

scholarly journals COMPARISON OF ESMOLOL, LABETALOL AND LIGNOCAINE FOR ATTENUATION OF SYMPATHOMIMETIC RESPONSES TO LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION

2019 ◽  
Vol 3 (7) ◽  
Author(s):  
Dr. H. Kirankumar
Keyword(s):  
Blood Pressure ◽  
Endotracheal Intubation ◽  
Stress Responses ◽  
Left Ventricular ◽  
Group Reduction ◽  
Group 3 ◽  
Group 2 ◽  
Artery Disease ◽  
American Society ◽  
Group 1

INTRODUCTION: In some individual’s suffering from hypertension, coronary artery disease, cerebrovascular disease, myocardial infarction and thyrotoxicosis, these hemodynamic stress responses can turn into life-threatening conditions like left ventricular failure, myocardial ischemia, cerebral hemorrhage, and ruptured cerebral aneurysm. Different drugs like lidocaine, vasodilator agents inhibiting sympathoadrenal response, α-and β-adrenergic blockers, and opioids can be administered prior to tracheal intubation to prevent hemodynamic responses. But higher dose of lignocaine may lead to hypotension, bradycardia, and hypoxia in patients. Due to various effect of these drugs on hemodynamic changes in patients this study was carried out to evaluate the effects of IV esmolol, lignocaine, and labetalol for attenuation of hemodynamic response to laryngoscopy and intubation. MATERIAL AND METHODS: A total of 90 consecutive patients were included in the study and were grouped in to, lignocaine group, labetalol and esmolol group containing 30 patients each. Age group 21–65 years of either sex or American Society of Anesthesiologists (ASA) Grade I or II scheduled for various general surgical procedures under endotracheal anesthesia were included in this study. Patients excluded were pregnant and lactating women, morbid obesity, and hypertension. RESULTS: Mean Age in Group 1, group2 and group 3 was 40.38 ± 7.25, 43.8 ± 9.24 and 42.56 ± 8.71 respectively while weight was 62.41 ± 7.32, 63.63 ± 8.11 and 60.74 ± 6.92 respectively. There were 17 male and 13 female in group 1, 19 male and 11 female in group 2 and 16 male and 14 female in group 3. Attenuation of blood pressure was more in labetalol group. Reduction of heart rate in labetalol group was significant. It is seen that Labetalol was more effective at attenuation of diastolic blood pressure among all drugs. Mean arterial pressure was not much reduced lignocaine and esmolol group as compared to labetalol. CONCLUSION: Haemodynamic alterations are usually observed during laryngoscopy and endotracheal intubation. In our study it was found that as labetalol is a safe and effective drug, for attenuation of sympathomimetic response.

In-vivo evaluation of the effect of cyanoacrylate on prosthetic vascular graft infection – does cyanoacrylate increase the severity of infection?

VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin
Keyword(s):  
Vascular Graft ◽  
Graft Infection ◽  
Vascular Graft Infection ◽  
Group 4 ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Prosthetic Vascular Graft Infection ◽  
Group 1

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.

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