Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes

Isolated thrombocytopenia after bone marrow transplantation was investigated in 65 fully engrafted patients surviving at least 60 days posttransplant. Twenty-four patients (37%) developed this complication, which occurred most frequently in patients receiving pretransplant preparation with total body irradiation or busulfan. Two distinct thrombocytopenic syndromes were identified: (1) transient thrombocytopenia (nine patients), in which a normal platelet count (greater than 100,000/microL) was initially established by day +40 but then diminished to less than 10,000 to 45,000/microL on day +40 to +70, with subsequent resolution of the thrombocytopenia by day +90; (2) chronic thrombocytopenia (15 patients), in which a platelet count greater than 100,000/microL was not achieved at any time during the first four months posttransplant, despite the simultaneous presence of normal granulocyte and reticulocyte counts. Although the transient syndrome did not adversely affect prognosis, the chronic syndrome carried a high mortality (21% actuarial survival at 1,000 days posttransplant compared with 67% survival for all patients, P less than .01) and had a high association with both severe (grades 3 to 4) acute graft-versus-host disease (GVHD) and chronic GVHD. In three of nine patients with transient thrombocytopenia, a temporal association with trimethoprim-sulfamethoxazole administration was observed, whereas in all other patients, no drug association could be found. Bone marrow biopsies in those patients with drug-associated thrombocytopenia showed decreased numbers of megakaryocytes, whereas biopsies in the remainder of the transiently thrombocytopenic patients demonstrated adequate numbers of platelet precursors, suggesting peripheral platelet destruction or ineffective thrombopoiesis. Biopsies in the chronic thrombocytopenic patients included those with and without adequate numbers of platelet precursors, although the association with chronic GVHD was strongest in patients demonstrating normal numbers of megakaryocytes. We conclude that isolated thrombocytopenia represents a significant complication of bone marrow transplantation, particularly in patients receiving hematopoietic ablative preparatory regimens, and that it is the chronic, not the transient, thrombocytopenic syndrome that is associated with an adverse patient prognosis.     

Functional and metabolic studies of polymorphonuclear leukocytes in the congenital Pelger-Huet anomaly

Polymorphonuclear leukocytes (PMNL) from two individuals with congenital Pelger-Huet anomaly (PHA) were examined to determine whether functional or metabolic defects accompanied the known morphological abnormality. No abnormalities of the PHA cells, as compared to normal control cells, were found when tested for quantitative leukocyte enzyme activities, nitroblue tetrazolium reduction, hexose monophosphate shunt activity, superoxide production, generation of chemiluminescence, or iodination. The PHA cells, as compared to normal PMNL, demonstrated normal chemotaxis and random migration, as well as bactericidal activity.     

A collaborative, double-blind randomized study of cetiedil citrate in sickle cell crisis

We have recently completed a double-blind, placebo-controlled, noncrossover study, the goal of which was to determine whether cetiedil citrate (cetiedil) could affect the course of vaso-occlusive crises in sickle cell disease. Patients, who presented to the emergency room at least 4 but no more than 24 hours after the onset of a painful vasoocclusive crisis severe enough to require hospitalization, were considered candidates for the study. Each patient received either placebo or cetiedil at one of the following three dosages: 0.2, 0.3, or 0.4 mg/kg body weight. The assigned drug dosage was given as a 30 minute intravenous infusion every 8 hours for 4 consecutive days. A total of 67 patients was enrolled in the study. Cetiedil, at its highest dosage (0.4 mg/kg body weight), was found to be significantly superior to placebo both in reducing the number of painful sites present on all 4 treatment days and in shortening the total time in crisis. No serious adverse reactions were observed during the course of the study. We conclude that cetiedil, given at a dosage of 0.4 mg/kg body weight, is therapeutically advantageous for sickle cell crisis.     

Clinical evaluation of a novel bipolar radiofrequency ablation system for renal masses

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? With the advancement of minimally invasive surgery, the management of small renal masses (SRM) has dramatically changed. Ablative technology such as radiofrequency ablation (RFA) and cryoablation have emerged as viable alternative modalities to extirpative surgery. RFA is one of the most studied and applied energy‐based, needle‐ablative treatment modalities, with encouraging mid‐ and long‐term oncological outcomes. Monopolar devices have several shortcomings. The electrodes are susceptible to the cooling effect of nearby blood vessels that act as a ‘heat sink’, limiting the extent of tissue ablation and forming lesions with asymmetric borders and ‘skip lesions’. Therefore, it is difficult to monitor and accurately predict the size of ablated lesions. A novel bipolar radiofrequency ablation (BRFA) device has been recently developed to address concerns with monopolar systems (Trod Medical, Paris, France). The BRFA system addresses the limitations of monopolar RFA, in terms of lesion size, targeting, consistency and concerns about cell death in the ablated area. We evaluated the BRFA device in 10 patients undergoing laparoscopic partial or radical nephrectomy. The present study demonstrates the safety and efficacy of a novel BRFA device. A BRFA device can produce a defined reproducible lesion with a precise transition zone to normal tissue. The area of ablated tissue exhibited completely devitalized cells and precise transition zone. With these characteristics, the potential advantages of this new technology during RFA ablation of SRM include less collateral damage and more complete ablation without skip lesions. This has the potential to lower rates of local recurrence and reduce incidence of skin burns. Further follow‐up studies are necessary to determine its oncological efficacy.

OBJECTIVE

• ? To evaluate a novel bipolar radiofrequency ablation (BRFA) system for the destruction of kidney tumours in patients.

MATERIALS AND METHODS

• ? Bipolar radiofrequency ablation (BRFA) was used to ablate renal masses in 10 patients undergoing laparoscopic radical or partial nephrectomy.
• ? The probe was placed percutaneously and laparoscopically guided into the tumour after routine laparoscopic exposure. The electrical current was continuously adjusted by the generator to overcome disruption from increasing impedance created from desiccated tissue.
• ? The specimens were then excised in routine fashion and analysed by a single pathologist.
• ? Lesion size and shape, and size of the transition zone to viable tissue were measured via nicotinamide adenine dinucleotide (NADH) staining.

RESULTS

• ? Ablation was successful in all 10 tumours. Mean time to set up and place the probe was between 2 and 4 min. Duration of ablation was 200 s.
• ? None of the ablated tissue showed signs of viable cells by histological examination and NADH staining.
• ? The mean size of the ablation zone was 6.26 cm³, with regular borders and a tapered cylindrical shape similar to the shape of the outer coil.
• ? The width of the transition zone, or area spanning complete tissue ablation to the first viable cells, ranged from 10 to 60 µm.
• ? There were no complications noted due to the ablation.

CONCLUSIONS

• ? A BRFA device can produce a defined reproducible lesion with a precise transition zone to normal tissue.
• ? The area of ablated tissue exhibited completely devitalized cells and precise transition zone.

     

Intracorporeal neobladder reconstruction: pressure-flow urodyamic studies in cadaveric orthotopic neobladders

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

? To determine the pressure‐flow characteristics of neobladders created in various configurations that may be constructed intra‐abdominally. Complete intracorporeal neobladder construction has been previously described but is limited due to excessive operative time and the need for an advanced laparoscopic skill set.

MATERIALS AND METHODS

? Four neobladder configurations were constructed, each using 20 cm of human cadaveric small intestine. The standard hand sewn Studer pouch was compared with a circular loop, W‐pouch, and U‐pouch with stapled anastamoses. ? Pressure flow studies were completed using the Aquarius TT UDS system (Laborie Medical Technologies, Toronto, Ontario) and each neobladder was filled to a pressure of 50 cm H2O. Neobladder change in pressure, capacity, and overall compliance were determined.

RESULTS

? The cystometric capacities of the stapled U‐pouch, W‐pouch, Circle pouch, and Studer pouch were 167.3 mL, 177.5 mL, 114 mL, and 145.2 mL respectively. The first increase in intravesical pressure was at 90.3 mL, 103 mL, 50 mL, and 85 mL. ? The greatest compliance of 3.81 mL/cmH2O was demonstrated in the U‐pouch, with the W‐pouch revealing a compliance of 3.44 mL/cmH2O. ? The least compliant neobladder was the circle pouch (2.24 mL/cmH20) followed by the standard Studer pouch (2.94 mL/cmH2O).

CONCLUSION

? The construction of an orthotopic neobladder must not only be technically feasible but maintain adequate capacity and compliance for optimal functioning. Pressure‐flow studies demonstrated equivalent results in alternate neobladder configurations. Additional data is needed to determine feasibility in vivo.     

A prospective, randomized study of the use of platelet concentrates irradiated with ultraviolet-B light in patients with hematologic malignancy

BACKGROUND: Irradiation of platelet concentrates (PCs) with ultraviolet- B (UVB) light inactivates the contaminating white cells and might be an alternative to filtration for the prevention of alloimmunization to HLA antigens and subsequent refractoriness to further platelet transfusions in multiply transfused patients with bone marrow failure. STUDY DESIGN AND METHODS: Patients with hematologic malignancy, mainly acute myeloid leukemia, were prospectively assigned in a random manner to receive either UVB-irradiated or control, nonirradiated PCs. All patients were given red cells that were white cell reduced by filtration. Transfusion efficacy and alloimmunization were assessed by means of corrected count increments, requirement for red cells and PCs, and measurement of lymphocyte-reactive antibodies. RESULTS: UVB-irradiated PCs had a clinical efficacy similar to controls as judged by corrected count increments at 1 to 6 and 12 to 24 hours and by the median requirement for red cell and platelet transfusions. Alloimmunization determined by measurements of lymphocyte-reactive antibodies using both conventional and antiglobulin-augmented lymphocytotoxicity techniques was not abolished in recipients of UVB-irradiated PCs (4/30, 13%) but was less than that in controls (5/20, 25%; p = NS). The mean number of platelet transfusion episodes prior to the occurrence of alloimmunization was greater in the control group (27 vs. 10; p = 0.017). CONCLUSION: In this trial, UVB irradiation did not diminish the clinical efficacy of platelet transfusions. There was a small but nonsignificant reduction alloimmunization, but no difference in refractoriness of the two groups was observed. Larger prospective randomized studies are required to confirm these findings and to compare UVB irradiation with white cell reduction.     

干细胞移植治疗缺血性心脏病的进展及其作用机制

学术背景：心肌梗死后，尽管现有的内外科治疗手段可以改善冠状动脉供血、挽救缺血心肌，但对已坏死的心肌或无功能心肌尚无良好治疗措施。细胞作为构成心脏结构、执行心脏功能的物质基础，尽管存在争议，但大量研究资料表明干细胞移植治疗是安全有效的。 目的：文章试图就目前成体干细胞在缺血，陛心脏病治疗的临床研究进展做一综述，客观评价成体干细胞治疗缺血性心脏病的安全性、有效性，阐述成体干细胞改善心功能的可能机制，介绍当今临床研究方向。 检索策略：由该论文的研究人员应用计算机检索Pubmed数据库1996／2007成体干细胞与缺血性心脏病方面的文献，检索词“adult stem cells,ischemial heart disease，cardiomyocytes”，并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1996／2007的相关文献，检索词“成年干细胞，心肌细胞，缺血性心脏病”，并限定文章语言种类为中文。共检索到1303篇文献，对资料进行初审，纳入标准：①文章所述内容应与缺血性心脏病干细胞移植密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准：①重复性研究。②Meta分析。 文献评价：文献的来源主要是通过对干细胞移植治疗缺血，陛心脏病现状及其作用机制进行汇总分析。1303篇文献中，动物实验和在体、离体、细胞学实验626篇，综述、述评、讲座类文献345篇，临床研究45篇，选用其中的46篇作为本文参考文献。 资料综合：①干细胞为一群具有自我更新、多向分化潜能的原始细胞，分为胚胎干细胞和成体干细胞。虽然研究表明胚胎干细胞较成体干细胞具有更强的增殖和分化潜能，但由于其涉及伦理道德、来源困难等原因，限制了它的使用。②就目前已完成的包括不同类型的成体细胞（如骨髓单个核细胞、内皮祖细胞、CD133^＋细胞、骨髓间充质干细胞、成肌细胞等）移植治疗缺血性心脏病的早期临床试验来看，尽管存在样本小、缺乏随机对照等不足，但均显示一个公认的事实，即无论采用何种方法移植成体干细胞治疗缺血性心脏病均是安全有效的。这对于正在进行的较大规模的临床研究是十分重要的，为其提供了更充分的临床资料。③多数研究认为干细胞改善心功能的作用机制包括直接与间接效应，如移植细胞横向分化为再生心肌与血管、移植细胞的旁分泌作用促进血管再生、抑制心肌细胞凋亡及心室重构等。近来研究认为外源前体移植心肌可以刺激机体内源心肌存留的干细胞增殖，从而改善心功能。 结论：尽管目前成体干细胞改善心功能的确切机制仍不清楚，但多数早期临床研究表明成体干细胞移植治疗缺血性心脏病是安全有效的。当前的研究方向是需要随机、双盲、安慰剂对照的多中心临床试验。     

Antigen-matched donor blood in the transfusion management of patients with sickle cell disease

BACKGROUND: Alloimmunization to red cell antigens is a significant risk in chronically transfused patients with sickle cell disease. Antigen matching, by decreasing the likelihood of alloantibody development, may significantly facilitate long-term management while decreasing morbidity. STUDY DESIGN AND METHODS: The transfusion records of 86 patients who underwent chronic transfusion for sickle cell disease at a tertiary-care medical center were reviewed retrospectively to determine the efficacy of an antigen-matching program in the prevention of alloimmunization to clinically significant red cell antigens. Recipients were phenotyped and given units matched for the K, C, E, S, and Fya or Fyb antigens. RESULTS: None (0%) of the 40 patients who received antigen-matched transfusions showed any evidence of alloimmunization, while 16 (34.8%) of the 46 patients who received both antigen-matched and non-antigen-matched transfusions developed clinically significant alloantibodies. The cost was 1.8 to 1.5 times that for a standard transfusion protocol. CONCLUSION: On the basis of this experience, it is recommended that transfusion centers engaged in the management of chronically transfused sickle cell anemia patients consider providing antigen-matched units for such patients. This is recommended not only because it prevents alloimmunization but also because such a program provides additional clinical benefits to the patient that may outweigh the higher costs of the process.