scholarly journals Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)

Kardiologiia ◽  
2020 ◽  
Vol 60 (11) ◽  
pp. 4-15
Author(s):  
V. Yu. Mareev ◽  
Ya. A. Orlova ◽  
A. G. Plisyk ◽  
E. P. Pavlikova ◽  
S. T. Matskeplishvili ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Clinical Status ◽  
Randomized Study ◽  
Lung Damage ◽  
Control Group ◽  
Virus Elimination ◽  
Combine Endpoint ◽  
Positive Polymerase Chain Reaction ◽  
Number Of Patients ◽  
Coronavirus Infection

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

scholarly journals Is Local Anesthetic Infiltration Prior to Intravenous Cannulation Beneficial to Patients?

2013 ◽  
Vol 8 (1) ◽  
pp. 10-13
Author(s):  
Babu Raja Shrestha ◽  
U Shrestha ◽  
A Shrestha ◽  
A Rana
Keyword(s):  
Heart Rate ◽  
Local Anesthetic ◽  
Randomized Study ◽  
Cardiovascular Responses ◽  
Control Group ◽  
Venous Cannulation ◽  
Number Of Patients ◽  
Group A ◽  
Group B ◽  
Local Anesthetic Infiltration

Aims: Intravenous cannulation causes pain, anxiety and frustration in patients along with changes in hemodynamic parameters. Infiltration of local anesthetic lessens the pain of intravenous cannulation. This study was performed to compare cardiovascular responses and verbal rating pain scores in two groups with and without local anesthetic infiltration prior to venous cannulation. Methods: This was a randomized study conducted in 100 elective surgical patients, divided into two study groups with 50 patients in each: group A (Control) and group B (local anesthetic infiltration). Prior to venous cannulation in group B, 0.5 ml of 1% lidocaine was infiltrated at the procedure site at dorsum of the wrist. Patients in group A were cannulated directly without local anesthetic infiltration. The hemodynamic changes pre and post cannulation and verbal pain rating scores were recorded by blind observers in all patients. Results: Demographic values in two groups were similar. Increase in heart rate from baseline value was significant in control group (p < 0.05). Post cannulation heart rate, systolic and diastolic blood pressure were significantly higher in group A compared to group B for the first three minutes (p < 0.05). Amongst higher number of patients in group A, verbal rating pain score was significantly higher. Ninety-four percent of the patients in group B were pain free, comfortable and satisfied with the procedure. Conclusions: Intravenous cannulation can be made pain free with patient satisfaction and hemodynamic stability if carried out with prior local anesthetic infiltration. Nepal Journal of Obstetrics and Gynaecology / Vol 8 / No. 1 / Issue 15 / Jan- June, 2013 / 10-13 DOI: http://dx.doi.org/10.3126/njog.v8i1.8853

Integral tests of the hemostasis system in assessing the efficiency of acetylsalicylic acid in patients with ischemic heart disease

2021 ◽  
Vol 67 (5) ◽  
pp. 427-433
Author(s):  
O.S. Melnichnikova ◽  
I.A. Nazarova ◽  
O.V. Sirotkina ◽  
A.V. Panov ◽  
I.T. Abesadze ◽  
...  
Keyword(s):  
Heart Disease ◽  
Acetylsalicylic Acid ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Area Under The Curve ◽  
Cardiovascular Complications ◽  
Control Group ◽  
Number Of Patients ◽  
Stable Cad ◽  
Analysis System

Despite the fact that acetylsalicylic acid (ASA) is the “gold” standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), a number of patients still have risks of atherothrombosis. In the present study, the antithrombotic effect of ASA in patients with CAD was assessed in platelet-rich plasma (PRP) using integral tests of the hemostasis study: the T-TAS system (Total Thrombus-formation Analysis System) and the thrombin generation test (TGT). The study involved 34 patients with stable CAD (11 women, 23 men) and people (15 women, 18 men) in the control group. As a result of assessing the activity of thrombus formation using the T-TAS system, a significant decrease in the area under the curve (AUC10) was found in the group with CAD patients compared with the control (135.6 [88.0-222.3] and 260.5 [217.3-301.9], respectively, p

scholarly journals Study comparing the stroke unit outcome and conventional ward treatment: a randomized study in Joinville, Brazil

2003 ◽  
Vol 61 (2A) ◽  
pp. 188-193 ◽  
Author(s):  
Norberto L. Cabral ◽  
Carla Moro ◽  
Giana R. Silva ◽  
Rosana Herminia Scola ◽  
Lineu César Werneck
Keyword(s):  
Hospital Stay ◽  
Stroke Unit ◽  
Survival Curve ◽  
Clinical Status ◽  
Randomized Study ◽  
Length Of Hospital Stay ◽  
General Ward ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

BACKGROUND AND PURPOSE: To assess the impact of a stroke unit (SU) on acute phase treatment when compared to a conventional general ward treatment (GW). METHOD: Seventy-four patients with acute stroke were randomized between a SU and conventional general ward (GW). We compared both groups regarding the length of hospital stay, lethality and functional and clinical status within 6 months, using the Scandinavian scale and Barthel index. RESULTS: Thirty-five and thirty-nine patients were allocated at SU and GW, respectively. Lethality on the 10th day at SU and GW achieved 8.5% and 12.8% respectively (p= 0.41), whereas 30-days mortality rates achieved 14.2% and 28.2% (p= 0.24), 17.4% and 28.7% on the 3rd month (p= 0.39), and 25.7% and 30.7% on the 6th month (p= 0.41). Thirty-day survival curve achieved 1.8 log rank (p= 0.17), with a trend for lower lethality in the SU. In order to save one death in 6 months in SU, NNT (the number need to treat) was 20; to get one more home independent patient NNT was 15. No significant difference was found between the length of hospital stay and morbidity. CONCLUSION: No significant benefit was found in SU patients compared to GW group. However,an evident benefit in absolute numbers was observed in lethality, survival curve and NNT in thirty days period after stroke. Further collaborative studies or incresead number of patients are required to define the role of SU.

Psychoeducational manual for treating binge eating disorder (BED) patients: A controlled trial

2011 ◽  
Vol 26 (S2) ◽  
pp. 730-730
Author(s):  
S.C. Stefano ◽  
A.M.R. Devoraes ◽  
A.M.R. Souza ◽  
M.H. Kaio ◽  
S.L. Blay
Keyword(s):  
Controlled Trial ◽  
Randomized Study ◽  
Outpatient Service ◽  
Care Program ◽  
Structured Interview ◽  
Stepped Care ◽  
Psychiatric Evaluation ◽  
Control Group ◽  
Comprehensive Treatment ◽  
Number Of Patients

ObjectiveTo evaluate the efficacy of a psychoeducational manual as first intervention when treating BED.MethodIt was conducted a 8-week controlled trial (before-after) without a control group. Twenty BED patients were enrolled at an outpatient service specialized in eating disorders (PROATA).After being submitted to a psychiatric evaluation and responding to the following instruments: MINI-PLUS, QEWP-R, BES, BDI, HAM-A, SF-36, and BSQ, the subjects signed a consent term and they received explanations about the manual. After eight weeks the patients were re-evaluated by trained examiners.The main outcome criterion was the BED evolution (evaluated through QEWP-R and BES). The secondary criteria were evaluated through the other instruments plus a semi-structured interview.ResultsMost patients presented a slight improvement of BED symptoms, although these symptoms are still present. The secondary criteria show that the most relevant aspect was that the information presented in the manual allowed the patients to acknowledge they had a condition and to see themselves with less guilt and prejudice, making it easier to look for a more comprehensive treatment.ConclusionsThere are indications that using the psychoeducational manual can reduce the symptoms, and that it can be useful in identifying the condition and allowing the patients to look for treatment. Also, since the instrument can be used as part of a stepped-care program, a broader, controlled and randomized study enrolling a larger number of patients must be conducted in order to better clarify the results.

scholarly journals Medical rehabilitation for coronavirus infection: new challenges for physical and rehabilitation medicine in Russia

2020 ◽  
Vol 97 (3) ◽  
pp. 14-21 ◽  
Author(s):  
A.A. Shmonin ◽  
M.N. Maltseva ◽  
E.V. Melnikova ◽  
I.E. Mishina ◽  
G.E. Ivanova
Keyword(s):  
Pulmonary Rehabilitation ◽  
Rehabilitation Medicine ◽  
Medical Rehabilitation ◽  
Lung Damage ◽  
Risk Of Infection ◽  
Physical And Rehabilitation Medicine ◽  
Number Of Patients ◽  
Infectious Disease Specialists ◽  
Coronavirus Infection ◽  
New Challenges

Coronavirus infection causes lung damage and leads to the development of disabling conditions. The development of the Covid-19 pandemic leads to a one-stage increase in the number of patients who need assistance not only from infectious disease specialists and intensive care specialists, but also from rehabilitation specialists. However, patients suffering from other non-infectious conditions need rehabilitation despite the pandemic. Thus, rehabilitation specialists are faced with new tasks to organize rehabilitation in the epidemic for both patients with Covid-19 and patients at high risk of infection, but without coronavirus infection, to develop specific programs for pulmonary rehabilitation, data collection on the nature of disability, organization of outpatient programs and telerehabilitation.

The effect of osteopathic correction on the function of external respiration in patients after COVID -19 coronavirus pneumonia

2021 ◽  
pp. 8-17
Author(s):  
A. F. Belyaev ◽  
T. S. Kharkovskaya ◽  
O. N. Fotina ◽  
A. A. Yurchenko
Keyword(s):  
Respiratory Function ◽  
Vital Capacity ◽  
Pathological Condition ◽  
The Body ◽  
Lung Damage ◽  
External Respiration ◽  
Single Procedure ◽  
Arterial Blood ◽  
Number Of Patients ◽  
Coronavirus Infection

Introduction. The 2019 coronavirus infection (COVID-19) pandemic caused by a novel coronavirus strain (SARS-CoV-2) posed a serious threat to public health around the world. Postcoid syndrome (post-COVID-19 condition, according to ICD-10 code U09 State after COVID-19 or Postcoid state, Postcoid syndrome) is a pathological condition after a coronavirus infection, accompanied by cardio-respiratory, neurological, musculoskeletal, metabolic disorders. According to a number of studies, osteopathic methods of correction increase the lymph flow, immunological protection of the body, help to reduce pain, reduce the restriction of mobility in the chest, and therefore improve the function of external respiration. There are practically no studies that allow assessing the effect of osteopathic correction methods on the function of external respiration at the modern evidence-based level in patients who have undergone COVID pneumonia.The aim was to study the effect of a single procedure of osteopathic correction on the function of external respiration in patients during the rehabilitation period after coronavirus pneumonia.Materials and methods. On the basis of the Primorsky Institute of Vertebroneurology and Manual Medicine (Vladivostok) the rehabilitation of patients after coronavirus pneumonia was carried out using osteopathic correction. The study included 73 patients over the age of 60 years with varying degrees of lung damage and impaired respiratory function. To assess the function of external respiration, spirometry was performed and the vital capacity of the lungs was assessed; pulse oximetry was performed to measure the saturation of arterial blood hemoglobin with oxygen (SpO2). Osteopathic testing and treatment were carried out according to clinical guidelines, and the biomechanics of the chest was additionally investigated. The Statistica-10 software package was used for the statistical analysis of the obtained data.Results. Osteopathic examination revealed the presence of local somatic dysfunctions in 98,8 % of patients (spinal dysfunction, rib dysfunction, diaphragm dysfunction). 87,6 % of patients were diagnosed with regional somatic dysfunctions of thoracic region. Global somatic dysfunctions were diagnosed in 78,4 % of patients. After a single procedure of osteopathic correction, patients had a statistically significant improvement of the external respiration function, manifested in an increase in vital capacity from 78,27±2,79 to 85,36±3,38 % (p=0,0006). Also, the effectiveness of osteopathic correction is confirmed by a significant increase in the average hemoglobin saturation of arterial blood with oxygen. Thus, in patients with low SpO2 levels, the index increased from 94,21±0,21 to 95,09±0,3 % (p=0,02). After a single osteopathic correction procedure, the number of patients with local somatic dysfunctions decreased from 98,8 to 17,7 %; global somatic dysfunctions were revealed only in 16,3 % of patients. All patients noted an improvement in their general condition, a decrease in symptoms of respiratory discomfort and shortness of breath, and an increase in chest excursion.Conclusion. A single procedure of somatic dysfunctions' osteopathic correction in patients after coronavirus pneumonia leads to a statistically significant improvement in respiratory function. The vital capacity and the oxygen saturation of the blood increase in patients. This is caused by the increase of the mobility of the chest (increase in its excursion), diaphragm, ribs, spine. The obtained results allow recommend the inclusion of osteopathic correction in the rehabilitation programs for patients who have undergone coronavirus infection.

scholarly journals Thiotriazolin effectiveness in complex treatment of patients with post-COVID syndrome

2021 ◽  
Vol 23 (3) ◽  
pp. 402-410
Author(s):  
V. I. Kryvenko ◽  
M. Yu. Kolesnyk ◽  
I. F. Bielenichev ◽  
S. V. Pavlov
Keyword(s):  
Antihypertensive Drugs ◽  
Thrombus Formation ◽  
Lung Damage ◽  
Control Group ◽  
Inclusion Criteria ◽  
Basic Therapy ◽  
X Ray ◽  
Standard Statistical Package ◽  
Microsoft Office ◽  
Pcr Test

The aim of this work is to evaluate the complex therapeutic effect of Thiotriazolin (anticoagulant, antiplatelet, metabolitotropic, endothelioprotective activity) in patients with post-COVID syndrome in comparison with basic therapy. Materials and methods. The studies involved 30 patients aged between 30 to 60 years with post-COVID syndrome. Of these, 15 persons received basic therapy (antibiotics, anticoagulants, acetylsalicylic acid), and other 15 patients received Thiotriazolin in the form of 200 mg tablets twice a day for 30 days against the background of basic therapy. Inclusion criteria were a positive PCR test for COVID-19; if the PCR test was negative, then the patients were enrolled based on the presence of IgM COVID-19 or IgG COVID-19 (with X-ray confirmed pneumonia). The rate of lung damage is up to 45 %. The patients had the following comorbidities: diabetes mellitus in the stage of compensation, arterial hypertension, ischemic heart disease without heart failure. The results of the study were calculated using the standard statistical package Statistica for Windows 13 (StatSoft Inc., № JPZ804I382130ARCN10-J), аs well as SPSS 16.0, Microsoft Office Excel 2003. Results. The inclusion of Thiotriazolin in the complex basic therapy of post-COVID syndrome led to a significant increase in the effectiveness of basic endothelioprotective, anticoagulant and antiaggregatory therapy and contributed to the prevention of thrombus formation. The administration of Thiotriazolin led to a significant improvement in general clinical parameters in patients with post-COVID syndrome – complaints of tachycardia disappeared, blood pressure was stabilized (without additional correction with antihypertensive drugs), weakness and increased fatigue disappeared. Saturation in 14 (93.4 %) patients increased to 97–98 %. In the control group only 7 (46.7 %) of 15 patients had oxygen saturation at 97–98 % level. Conclusions. The introduction of the drug Thiotriazolin in the form of 200 mg tablets twice a day for 30 days into the complex basic therapy of post-COVID syndrome leads to a significant increase in the basic endothelioprotective, antiaggregatory and anticoagulant therapy and contributes to the prevention of thrombus formation against the background of improving the state of the myocardium and vascular endothelium.

scholarly journals Novel coronavirus infection (COVID-19) in tuberculosis patients in St. Petersburg

2021 ◽  
Vol 13 (2) ◽  
pp. 38-43
Author(s):  
E. A. Malashenkov ◽  
S. V. Gudova ◽  
D. A. Gusev ◽  
I. P. Fedunyak ◽  
E. L. Denisova ◽  
...  
Keyword(s):  
Mutual Influence ◽  
Molecular Genetic ◽  
Active Phase ◽  
Clinical Infectious Disease ◽  
Negative Influence ◽  
Lung Damage ◽  
Polymerase Chain Reaction Test ◽  
Positive Polymerase Chain Reaction ◽  
Coronavirus Infection ◽  
Novel Coronavirus

The aim of this work was to attempt to analyze the demographic structure, clinical and radiological forms of tuberculosis and COVID-19, as well as the course and outcome of the disease in patients with this coinfection in the light of a new and still poorly understood problem of the mutual influence of tuberculosis and COVID-19.Material and methods. Examination and treatment were carried out in the infectious-tuberculosis departments of the Botkin Clinical Infectious Disease Hospital. We examined 63 patients identified in the first seven months of the epidemic in the multimillion city of St. Petersburg (Russia). Tuberculosis, confirmed by conventional bacteriological and molecular genetic methods, had an active phase in all of them. The new coronavirus infection was verified by a positive polymerase chain reaction test for SARS-CoV-2.Results. Tuberculosis in 43 patients was detected simultaneously with COVID-19, in 20 people it preceded coronavirus infection. Disseminated forms of tuberculosis prevailed - 50.8%; in 36.5%, two or more organs and systems were affected, which is associated with a high proportion (54.0%) of HIV-positive patients with an advanced stage of the disease. Lung damage with COVID-19 was noted in 36.5%. Fatal outcomes ended in 20.6% of cases of coinfection, the structure of the causes of death is given.Conclusion. An assumption was made about the possibility of an aggravating effect of tuberculosis on COVID-19 in the case of severe or widespread forms of these diseases. The negative influence of HIV infection on the outcome of the disease has also been shown. Further follow-up is required to identify more reliable associations between tuberculosis and COVID-19. 

scholarly journals Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study)

Kardiologiia ◽  
2020 ◽  
Vol 60 (6) ◽  
pp. 15-29 ◽  
Author(s):  
V. Yu. Mareev ◽  
Ya. A. Orlova ◽  
E. P. Pavlikova ◽  
S. T. Matskeplishvili ◽  
T. N. Krasnova ◽  
...  
Keyword(s):  
Treatment Group ◽  
Lung Injury ◽  
Thrombus Formation ◽  
Clinical Status ◽  
Pulse Therapy ◽  
Control Group ◽  
Autoimmune Inflammation ◽  
Anti Inflammatory ◽  
High Doses ◽  
D Dimer

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as “cytokine storm”, and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients’ condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001).Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.

Pentostatin, Tacrolimus, and “Mini”-Methotrexate for Graft-Versus-Host Disease (GVHD) Prophylaxis: A Phase I/II Controlled, Randomized Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 727-727
Author(s):  
M. de Lima ◽  
D. Couriel ◽  
M. Munsell ◽  
M. Westmoreland ◽  
H. Shah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Treatment Plan ◽  
Randomized Study ◽  
Dose Finding ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Intention To Treat ◽  
Gvhd Prophylaxis ◽  
Number Of Patients ◽  
Risk Patients

Abstract GVHD remains a major obstacle to a successful unrelated (UD) or mismatched related (MRD) donor hematopoietic stem cell transplantation (HSCT). Pentostatin is a purine nucleoside analog that targets adenosine deaminase and leads to lymphocyte depletion, with low potential for myelosuppression. We are investigating the incorporation of pentostatin to our standard GVHD prophylaxis regimen with tacrolimus (tacro) and methotrexate (MTX). Methods: This is an adaptive randomized, dose finding study that takes into account toxicity and efficacy in a Baysean “play the winner” design. The “winner” dose moves to the phase II portion of the study. Probability of assignment to the control group was fixed at 20%. Recipients of UD and MRD are eligible; all analysis is done by intention to treat. Success was defined as being alive, engrafted, in complete remission(CR), without GVHD at study completion (100 days post HSCT). Development of grade III-IV acute (a) GVHD defined failure at any time, while grade I–II did not constitute failure if absent by day 100. This design has power 0.7 to detect a dose that has a success rate of 60% for low-risk patients (HLA matched, in CR) and 45% for high-risk patients (mismatched, not in CR). High-resolution typing was available for all donor-recipient pairs at HLA-DRB1 and -DQB1 loci, and to 83% of the pairs at HLA-A and -B loci; all patients had low-resolution -C typing. Treatment plan: tacro from day -2 (target level of 5–15 ng/ml) and MTX 5 mg/m2 on days +1, +3, +6 to all patients; day +11 was given only to the control group. Pentostatin was given on days +8, +15, +22 and +30, in treatment arms: 0.5 mg/m2, 1 mg/m2, 1.5 mg/m2, and 2 mg/m2. Results: 73 patients, median age 45 yrs (range 18–72) have been enrolled. Diagnosis were AML/MDS(n=48), ALL(n=8), CML (n=10) and NHL(n=7); 58% of the patients were not in CR at HSCT. Conditioning regimens were busulfan based(n=52), melphalan based(n=10), BEAM(n= 2), and CyTBI(n =9); 71% were ablative and 29%, reduced intensity. ATG was used in the regimen in 86% of the cases. Stem cell source: bone marrow (n=67) and peripheral blood(n=6). Donors: UD(n=67) and MRD(n=6). Proportion of patients with donor-recipient HLA mismatches was 24%, 20%, 33%, 21% and 40%, respectively for the 5 study arms; median age was similar. 85% of the intended pentostatin doses were delivered. Pentostatin did not delay engraftment. Incidence of toxicities (control vs. study arms): renal (all grade I/II)=47% vs 36%; TTP/HUS= 12% vs 9% (more severe among pentostatin patients); early relapse= 12% vs 5%; engraftment failure=6% vs 3%; delayed engraftment (>21 days): 0 vs. 5%. Probability that dose 1.5 mg/m2 is better than control is 0.9341. Pentostatin dose control group (n=17) 0.5 mg/m2 (n=10) 1 mg/m2 (n=12) 1.5 mg/m2 (n=24) 2 mg/m2 (n=10) gd II-IV aGVHD 47% 44% 63% 29% 50% gd III-IV aGVHD 20% 33% 27% 10% 10% CMV reactivation 41% 30% 33% 50% 50% bact/fungal infection 59% /12% 60% /10% 50% /18% 55% /17% 70% /10% Not evaluable n=2 n=1 n=1 n=4 n=0 Failure rate 47% 70% 33% 29% 40% Conclusions: This preliminary analysis indicates that aGVHD rate may be reduced with pentostatin 1.5 mg/m2, without interference with engraftment. Longer follow-up and larger number of patients will be needed to assess impact on survival.

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