Enzyme pathology of human mesotheliomas.

In samples of 16 surgically resected mesotheliomas arising from the pleura of the human lung, 6 enzymes from different metabolic pathways, DNA, and mitotic frequency were quantified. The mesotheliomas, irrespective of cell type or grade, showed lower gamma-glutamyl transpeptidase (GGT) concentration than 36 of the 38 pulmonary adenocarcinomas. The mean concentration of this enzyme in the 15 mesotheliomas was an eighth of that in the 56 carcinomas, whereas their DNA content was similar. The quantitative correlation of thymidine kinase (TK), uridine kinase (UK), and phosphoserine phosphatase to mitotic frequency was highly significant for mesotheliomas, as well as for carcinomas. As estimated from their TK [and its recently established quantitative correlation to volume doubling time (DT)], the DT of the 16 mesotheliomas ranged from 50 to over 700 days, with a somewhat longer median than the median for pulmonary carcinomas. Subject survival, though shortest for the 2 sarcomatous mesothelioma cases, varied over an overlapping range for mesotheliomas with epithelial or mixed cell type. The biopsy samples' TK and UK concentrations, however, showed a significant inverse correlation with months of survival after diagnosis. Survival time after the first appearance of symptoms decreased linearly (on log scales) with TK concentration (P less than .001) over the 14 cases. The results of this first quantitative study of a spectrum of biochemical constituents of mesotheliomas identify GGT as an enzyme whose measurement guards against mistaking mesotheliomas and adenocarcinomas for one another and show that the TK concentrations of these mesothelioma samples bear a highly significant, inverse correlation to the postdiagnosis survival time of the individual subjects.

Uridine kinase, adenylate kinase, and guanase in human lung tumors.

In pulmonary neoplasms, the uridine kinase concentration was higher (2- to 20-fold) than in the noninvolved lung portions of each of the 12 subjects studied. The extent of elevation of uridine kinase in the different tumors showed a significant positive correlation with the rises (1.5- to 30-fold) in thymidine kinase, suggesting that neoplastic transformation in human lung involved coordinated increases in the capacity for the reutilization of different nucleoside phosphates. Adenylate kinase was always at lower levels in neoplasms compared to noninvolved areas of the same lung, and the extent of this loss in the different tumors correlated inversely with the gain in uridine kinase and thymidine kinase. Normal fetal human lung was also deficient in adenylate kinase, while its uridine kinase and thymidine kinase (and also guanase) activities were above the adult levels. The guanase activities of the different neoplasms, unrelated to their uridine kinase or thymidine kinase content, correlated with the activities in the subjects' noninvolved lung. These individual differences were much more striking than those between the neoplastic and control samples. Variations in guanase activity thus appear to be "random," whereas observations on the three other enzymes attest to the orderly nature of biochemical differences among individual tumors and between normal and neoplastic lung.

Pulmonary carcinoid tumors: enzymic discriminants, growth rate, and early age of inception.

Analyses of enzymes from various metabolic pathways in pulmonary carcinoid tumors and radiological measurements of their volume increase were compared with those for lung carcinomas of various cell types. The results describe new biochemical features in carcinoid tumors, present the first quantitative evidence for their slow growth rate (i.e., long doubling time) in vivo, and show that measurement of 2 or 3 appropriate enzymes in biopsy samples can guard against instances in which carcinoids and adeno- or oat cell carcinomas are mistaken for one another on histological examination. The uridine kinase to thymidine kinase ratio as well as the beta-galactosidase concentration of carcinoid tumors were 5 times higher than of carcinomas, and their gamma-glutamyl transpeptidase was below that of all 35 adeno- and the 11 squamous cell carcinomas. Thymidine kinase, which bears a quantitative inverse correlation to volume doubling time (irrespective of cell type), had much lower titers in the 9 carcinoids than in the 6 oat cell carcinomas and reflects most clearly their very different (despite common histogenesis) clinical malignancy. Owing to their long doubling time, carcinoid tumors on the average required a much longer period (40.5 years) to attain final volume than did carcinomas (17.8 years). The calculated mean age of the subjects when growth began, -0.5 years (as opposed to 51 years for carcinomas), suggests a prenatal or early childhood inception for pulmonary carcinoid tumors.

Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients.

PURPOSE: To determine the value of pretransplant studies in predicting day 100 nonrelapse toxic mortality following high-dose therapy. PATIENTS AND METHODS: A retrospective review of 383 consecutive hematopoietic stem-cell transplants was performed with attention to toxic mortality and pretransplant factors. Univariate log-rank analysis was used to yield the most significant cut-off values for individual factors. Multivariate analysis using Cox proportional hazards regression determined factors independently predictive of early toxic death. RESULTS: Nonrelapse toxic mortality before day 100 occurred in 23 of 383 (6.0%) transplant recipients. Factors associated with an increased risk of toxic death by univariate analysis included forced expiratory volume in 1 second (FEV1) less than 78% of predicted (P = .0002), allogeneic versus autologous transplant (P = .0003), diffusion capacity of carbon monoxide less than 52% of predicted (P = .002), serum creatinine concentration greater than 1.1 mg/dL (P = .003), Eastern Cooperative Oncology Group performance status greater than 0 (P = .006), preparative regimen containing total-body irradiation versus chemotherapy alone (P = .006), marrow versus blood stem cell (P = .01), serum ALT greater than 50 IU/L (P = .02), diagnosis of hematologic disorder versus solid tumor (P = .06), serum bilirubin level greater than 1.1 mg/dL (P = .08), left ventricular ejection fraction (P = .09), and growth factor use (P = .09). In the multivariate model, transplant type (relative risk, 4.2), FEV1 (relative risk, 4.5), performance status (relative risk, 3.7), serum creatinine (relative risk, 3.8), and serum bilirubin (relative risk, 3.7) were found to be independent predictors of early toxic mortality. CONCLUSION: The pretransplant evaluation is a useful tool to identify patients at risk for early toxic mortality following high-dose therapy.

Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial.

PURPOSE: It is well-established that the infusion of hematopoietic growth factors (HGF) accelerates neutrophil recovery in patients undergoing high-dose therapy followed by autologous bone marrow infusion. In addition, there is evidence that the infusion of autologous peripheral-blood stem cells (PBSC) accelerates engraftment in comparison to patients who receive bone marrow alone. However, few data are available regarding the ability of HGF to accelerate engraftment further in patients who receive PBSC following high-dose therapy. PATIENTS AND METHODS: Forty-one patients undergoing high-dose therapy followed by infusion of autologous PBSC with or without bone marrow were randomized to receive granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg/d beginning on day + 1 following transplant or standard posttransplant supportive care without HGF. RESULTS: The median time to a neutrophil count > or = 500/microL was 10.5 days in the G-CSF group versus 16 days in the control group (P = .0001). G-CSF was associated with statistically significant reductions in the time to neutrophil engraftment among patients who received PBSC alone (11 v 17 days, P = .0003) and in patients who received PBSC in conjunction with bone marrow (10 v 14 days, P = .02). The median duration of posttransplant hospitalization (18 v 24 days, P = .002) and the median number of days on nonprophylactic antibiotics (11 v 15, P = .03) were also significantly reduced. CONCLUSION: Administration of G-CSF in the posttransplant period accelerates the rate of neutrophil engraftment, shortens the duration of hospitalization, and reduces the number of days on nonprophylactic antibiotics in patients who receive autologous PBSC with or without autologous bone marrow following high-dose therapy.

A novel strategy for stent deployment in the treatment of acute or threatened closure complicating balloon coronary angioplasty. Use of short or standard (or both) single or multiple Palmaz-Schatz stents.

OBJECTIVES: The purpose of this study was to determine the immediate and long-term angiographic and clinical results of coronary stenting as a specific therapy for intracoronary dissection associated with acute or threatened closure complicating percutaneous transluminal coronary angioplasty. BACKGROUND: Published reports contain conflicting results with regard to the benefit of stent insertion for coronary dissection. In particular, there is a wide range in the reported rates of subacute occlusion. METHODS: Palmaz-Schatz stents were inserted in 56 patients who had significant dissections and acute or threatened closure complicating coronary angioplasty. An attempt was made to cover the entire site of the dissection with short or standard single or multiple Palmaz-Schatz stents. The use of the short stent allowed complete coverage of the dissection, specifically in situations such as marked vessel tortuosity or the need to place a stent distal to a deployed stent. RESULTS: A single stent was implanted in 24 patients and multiple stents were implanted in 32 patients. A total of 138 stents (78 standard, 60 short stents) were implanted. The primary clinical success rate was 88% (49 of 56 patients). Complications occurred in seven patients (12.5%): Three patients (5%) required urgent bypass surgery; two patients (4%) had a myocardial infarction; and two patients (4%) died. Subacute occlusion occurred in one patient (2%). Clinical follow-up was available in all patients at a mean of 10 +/- 4 months. Thirty-nine (80%) of 49 patients were clinically asymptomatic. Angiographic restenosis was found in 15 (36%) of 42 patients on angiographic follow-up performed a mean of 5 months (median 6) after the procedure in 86% of the eligible patients. Nine patients had successful repeat angioplasty, and two had elective bypass surgery. CONCLUSIONS: The strategy of coronary stenting to completely cover the lesion is an effective treatment for large coronary dissection complicating angioplasty. A total major complication rate of 12.5% may be acceptable for this high risk group.

Benefit of intracoronary ultrasound in the deployment of Palmaz-Schatz stents.

OBJECTIVES: This study was designed to evaluate the changes in intrastent and angiographic dimensions when intravascular ultrasound imaging is used to direct the deployment of balloon-expandable Palmaz-Schatz stents in coronary arteries and saphenous vein grafts. BACKGROUND: Intravascular ultrasound provides more information than angiography in the imaging of intravascular structures. Previous studies have shown that obtaining a larger lumen (greater "acute gain") with coronary interventions such as stenting leads to less restenosis and subacute thrombosis. It is not clear whether the information obtained by intravascular ultrasound can be used to obtain a greater acute gain in lumen dimensions. METHODS: Forty consecutive patients undergoing Palmaz-Schatz stent implantation had intravascular ultrasound imaging performed after a good angiographic appearance was obtained. If the stent did not appear adequately expanded by intravascular ultrasound, or if the struts were poorly apposed to the arterial wall, further stent dilation with larger balloons or higher pressure inflations were performed. Twenty-nine patients had subsequent intravascular ultrasound imaging. Intrastent diameters and areas were compared from the initial to the final intravascular ultrasound studies. RESULTS: Of the 40 patients studied, only 5 (13%) had an adequate result by intravascular ultrasound despite an acceptable angiographic appearance in all patients. Six additional patients did not undergo subsequent intravascular ultrasound imaging. The other 29 patients all demonstrated a significant increase in intrastent minimal diameter (mean 19%), major diameter (11%) and cross-sectional area (34%) (p < 0.001 for all measurements). CONCLUSIONS: The use of intravascular ultrasound imaging in the deployment of balloon-expandable Palmaz-Schatz stents leads to a significant increase in intrastent dimensions (greater "acute gain").

Predictors of diffuse and aggressive intra-stent restenosis.

OBJECTIVES: This study was performed to investigate the causes of diffuse and aggressive intra-stent restenosis. BACKGROUND: Although restenosis is usually considered to be a dichotomous variable, there is clinical relevance to the severity of restenosis. It is not known which variables are predictive of diffuse or aggressive intra-stent restenosis. METHODS: A consecutive series of 456 coronary lesions with in-stent restenosis was evaluated for the type of restenosis using quantitative coronary angiography. Restenosis was defined as > or = 50% diameter stenosis at follow-up angiography, diffuse restenosis as a follow-up lesion length > or = 10 mm and aggressive restenosis as either an increase in lesion length from the original lesion or a restenotic narrowing tighter than the original. Clinical, anatomic and procedural characteristics were evaluated for lesions associated with these types of restenosis. RESULTS: Diffuse restenosis was associated with a smaller reference artery diameter, longer lesion length, female gender, longer stent length and the use of coil stents. Aggressive restenosis was more common in women, with the use of Wallstents and with long stent to lesion length ratios. Aggressive restenosis occurred earlier and was more closely associated with symptoms and myocardial infarctions than nonaggressive restenotic lesions. CONCLUSIONS: Markers for diffuse restenosis were also important markers for the presence of any restenosis. A long stent to lesion length ratio is an important marker for aggressive restenosis. When severe forms of in-stent restenosis occur, they tend to present earlier and with more symptoms, including myocardial infarction. More careful consideration of the type of in-stent restenosis may aid in identifying when alternative strategies may be useful.

Intracoronary stent insertion after balloon angioplasty of chronic total occlusions.

OBJECTIVES: This retrospective analysis was performed to assess the medium-term effectiveness of implanting intracoronary stents into chronic total occlusions that are successfully opened by balloon angioplasty. BACKGROUND: The value of percutaneous transluminal coronary angioplasty of chronic total occlusions is limited by a very high restenosis rate of 50% to 68%. Intravascular stents have been shown to reduce restenosis in a subset of patients with subtotal stenoses. It has not been demonstrated that the placement of stents into successfully opened chronic total coronary artery occlusions leads to lower rates of restenosis. METHODS: A consecutive series of patients with chronic total coronary occlusions successfully opened by balloon angioplasty received Palmaz-Schatz stents. Patients underwent clinical and angiographic follow-up at a mean of 6 months after stent insertion. Angiographic and clinical results were retrospectively analyzed. RESULTS: Fifty-nine patients underwent stenting of 60 chronic total coronary occlusions, with a 98% rate of successful stent deployment. Complications occurred in 5% of cases, all with subacute thrombosis. Angiographic follow-up was obtained in 88% of patients at a mean of 6 months and demonstrated an angiographic restenosis rate of 20%, with only one reocclusion. Among several variables examined, only the presence of a procedure-related moderate to severe dissection was associated with higher follow-up percent diameter stenoses and clinical events. At a mean of 14 months after stent insertion, 77% of patients remained free of symptoms or clinical events. CONCLUSIONS: The implantation of intracoronary stents into vessels with opened chronic total coronary occlusions is associated with favorable rates of angiographic restenosis and relief of symptoms. A randomized clinical trial comparing balloon angioplasty with stent-assisted balloon angioplasty in the treatment of chronic total coronary occlusions is indicated.

Comparison of aggressive versus nonaggressive balloon dilatation for stent deployment on late loss and restenosis in native coronary arteries.

Aggressive balloon dilatation is currently performed to assure full stent expansion and minimize the risk of stent thrombosis. It is not known if aggressive stent expansion leads to further increases in intimal proliferation and restenosis. A retrospective analysis was performed of 688 consecutive coronary narrowings in which stents were implanted. Angiographic follow-up was performed and quantitative coronary angiographic measurements were obtained using electronic calipers. Patients were divided into 2 groups. Group A (212 narrowings) had stents implanted before 1993, before the routine use of aggressive stent expansion techniques. Group B (476 narrowings) had stents implanted after 1993, when oversized balloons or high-pressure inflations were performed inside stents. Comparisons were made between angiographic changes and clinical outcomes between the 2 groups. Group B lesions had less favorable characteristics due to longer lengths of lesions. Despite this there was less angiographic and clinical restenosis in this cohort. There was no difference in late loss between the 2 groups. Thus, aggressive stent implantation techniques were not associated with increased late loss or restenosis.

Intravenous three-dimensional coronary angiography using contrast enhanced electron beam computed tomography.

Coronary angiography remains the diagnostic standard for establishing the presence, site, and severity of coronary artery disease (CAD). Electron beam computed tomography (EBCT), with its 3-dimensional capabilities, is an emerging technology with the potential for obtaining essentially noninvasive coronary arteriograms. The purpose of this study was to (1) test the accuracy of intravenous coronary arteriography using the EBCT to conventional coronary arteriographic images; (2) establish the inter-reader variability of this procedure; (3) determine the limitations due to location within the coronary tree; and (4) identify factors that contributed to improved image quality of the 3-dimensional EBCT angiograms. Fifty-two patients underwent both EBCT angiography and coronary angiography within 2 weeks. The coronary angiogram and the EBCT 3-dimensional images were analyzed by 2 observers blinded to the results of the other techniques. EBCT correctly identified 43 of 55 significantly stenosed arteries (sensitivity 78%), and correctly identified 118 of 130 of the nonobstructed arteries, yielding a specificity of 91% (p <0.001, chi-square analysis). The overall accuracy for EBCT angiography was 87%. Significantly more left main and anterior descending coronary arteries were adequately visualized than the circumflex and right coronary vessels (p = 0.003). Overall, 23 of 208 (11%) major epicardial vessels were noninterpretable by the blinded EBCT readers, primarily due to motion artifacts caused by cardiac and respiratory motion and poor electrocardiographic gating. The inter-reader variability was similar to that of angiography, and its high accuracy makes this a clinically useful test. This study demonstrates, by using intravenous contrast enhancement, that EBCT can clearly depict the coronary artery anatomy and can permit identification of coronary artery stenosis.

Bilateral spontaneous pneumothoraces caused by metastatic ovarian granulosa cell tumor.

A case is presented of a woman with bilateral spontaneous pneumothorax and pulmonary metastases originating from an ovarian granulosa cell tumor. It is the first known case report of an association between these two entities described in the English literature.

Post-irradiation somnolence syndrome in an adult patient following allogeneic bone marrow transplantation.

Neurologic disturbances are common following the intensive chemotherapy and radiotherapy of bone marrow transplantation (BMT) conditioning regimens. The somnolence syndrome, which occurs in most children treated for leukemia with prophylactic cranial irradiation, has previously not been reported following BMT. This syndrome consists of transient lethargy, irritability, headaches, low grade fevers, gastrointestinal disturbances and depression. We report the case of a 38-year-old female with acute non-lymphocytic leukemia who developed symptoms typical of the somnolence syndrome 8 weeks following 1320 cGy total body irradiation and cyclophosphamide conditioning. Encephalographic findings were consistent with the syndrome, and no additional infectious or metabolic disorders could be identified. As predicted by the pediatric experience, the symptoms were transient, resolving following steroid and anti-depressant therapy. Among patients undergoing radiation based conditioning regimens, especially those not receiving concurrent steroid therapy, the appearance of post-transplantation somnolence may be an expression of this syndrome.

Association between antibodies reactive with neutrophils, rate of neutrophil engraftment, and incidence of post-engraftment neutropenia following BMT.

Previous reports have suggested that antibodies reactive with neutrophils (ARN) are frequently detectable in patients undergoing bone marrow or blood stem cell transplantation (BMT), and that such antibodies result in steroid-responsive delayed neutrophil engraftment or steroid-responsive post-engraftment neutropenia in some patients. However, the true incidence and significance of ARN in the BMT setting remain poorly established because most of the published data are in the form of retrospective case reports. Therefore, we prospectively studied the incidence of ARN, the rate of neutrophil engraftment, and the incidence of post-engraftment neutropenia in a cohort of 40 BMT candidates. Sixteen of the 36 evaluable patients (44%) had detectable ARN following transplant vs none of 25 concurrently studied healthy controls (P < 0.0001). Patients with detectable ARN in the post-transplant period recovered to an absolute neutrophil count (ANC) of 500 x 10(9)/l a median of 3.5 days later than patients without detectable ARN; multivariate analysis controlling for the potential effects of diagnosis, conditioning regimen, amount of prior therapy, and other factors revealed that only the administration of hematopoietic growth factors (P = 0.008) and the presence of ARN in the post-transplant period (P = 0.016) were independently predictive of the rate of neutrophil engraftment following BMT. Four of the 16 patients with detectable ARN (25%) satisfied previously published criteria for post-engraftment neutropenia, ie a fall in the ANC to less than 500 x 10(9)/l for at least 2 consecutive days, following initial engraftment to an ANC of at least 1000 x 10(9)/l for at least 2 consecutive days. In contrast, none of the 20 patients without detectable post-transplant ARN developed post-engraftment neutropenia. Multivariate analysis revealed that only the presence of ARN in the post-transplant period (P = 0.022) was independently predictive of post-engraftment neutropenia. All four patients with ARN-associated post-engraftment neutropenia responded to steroid-based therapy. These prospectively gathered data support previously published primarily case report data suggesting that ARN occur frequently following BMT and are associated with an increased incidence of delayed neutrophil engraftment and post-engraftment neutropenia. As is the case in the non-transplant setting, ARN-associated neutropenia occurring following BMT may respond to steroid-based therapy.

Treatment of hepatic veno-occlusive disease with low-dose tissue plasminogen activator: impact on coagulation profile.

An 18-year-old white male developed severe hepatic veno-occlusive disease (VOD) during an autologous bone marrow transplant for primary refractory nodular sclerosing Hodgkin's disease. As a result of VOD-induced hepatic dysfunction, coagulation studies revealed depression of vitamin K dependent procoagulant factor VII. Intravenous recombinant tissue plasminogen activator 20 mg over h on 4 consecutive days and continuous heparin infusion (1000 unit bolus followed by 150 units/kg/day) resulted in rapid reversal of the VOD syndrome. During treatment, procoagulant factors II, VII, IX and X levels increased indicating the return of hepatic synthesizing capacity. Factor V levels, which were elevated pre-therapy, also rose dramatically. Plasma antigen levels of protein C, a natural anticoagulant, remained severely depressed. No clinical evidence of bleeding and only minimal systemic fibrinolysis was noted. Despite concerns regarding the use of lytic therapy in a thrombocytopenic post-BMT patient, serial measurements of coagulation parameters during severe VOD suggested that low dose rt-PA improved portions of the systemic hemostatic profile.

Phase II study of high-dose cyclophosphamide, etoposide, and carboplatin (CEC) followed by autologous hematopoietic stem cell rescue in women with metastatic or high-risk non-metastatic breast cancer: multivariate analysis of factors affecting survival and engraftment.

Seventy women with high-risk stage II (n = 10), IIIA (n = 12), IIIB (n = 11), or IV (n = 37) breast cancer received cyclophosphamide 6000 mg/m2, etoposide 2400 mg/m2, and carboplatin 1200 mg/m2 followed by infusion of autologous hematopoietic stem cells (AHSC). Women with high-risk stage II disease had eight or more involved axillary lymph nodes (n = 9) or axillary and breast relapse following lumpectomy, chemotherapy, and radiation therapy (n = 1). Women with measurable stage III or stage IV disease were required to demonstrate complete or partial response to conventional-dose chemotherapy prior to transplant. The overall (complete plus partial) response rate for the 31 patients not in complete remission at the time of transplant was 55%. With a median follow-up of 545 days, the 2-year actuarial progression-free survival rates for patients with stage II, IIIA, IIIB and IV are 86, 75, 42 and 13%, respectively. Factors independently predictive of longer progression-free survival by multivariate analysis included lower stage disease, status of disease at transplant (in CR vs not in CR), and positive estrogen receptor status. Factors predictive of more rapid neutrophil engraftment by multivariate analysis included post-transplant administration of hematopoietic growth factors, greater number of infused CFU-GM, mobilization with G-CSF or cyclophosphamide/G-CSF (vs mobilization with GM-CSF or no mobilization), and lower stage disease. Only one patient (1.4%) died prior to day 100 from any cause. High-dose cyclophosphamide, etoposide, and carboplatin followed by infusion of AHSC constitutes an active and well-tolerated regimen in the treatment of women with high-risk non-metastatic or metastatic breast cancer.

Treating refractory chronic graft-versus-host disease with extracorporeal photochemotherapy.

Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy, has previously demonstrated promising results in treating chronic graft-versus-host disease (cGvHD). We treated six patients (ages 33-54 years) with long-standing refractory extensive-stage cGvHD. ECP was performed thrice weekly initially in all patients. Concomitant therapies included prednisone (n=6), tacrolimus (n=5), cyclosporin A (n=2), hydroxychloroquine (n=2), mycophenolate mofetil (n=1), and psoralen plus ultraviolet A radiation (n=1). After an average of 7.2 months (range, 2-13 months) of ECP, all patients experienced either improvement or stabilization in sclerodermatous skin changes, as well as partial improvements in liver enzyme levels. Skin softening occurred in four patients and was noted as early as 3-8 weeks into treatment. Two patients were able to taper steroid therapy, and two patients were able to taper ECP to twice weekly. ECP was well tolerated. Our results support those of previous studies, suggesting that ECP may be beneficial in patients with refractory cGvHD.

Treatment of leukemic relapse following unrelated umbilical cord blood transplantation with interleukin-2: potential for augmenting graft-versus-leukemia and graft-versus-host effects with cytokines.

In comparison to bone marrow, umbilical cord blood has decreased intrinsic immune responsiveness allowing transplantation across HLA barriers with lower rates of graft-versus-host disease. However, laboratory models have also suggested that cord blood may be extremely sensitive to stimulation by cytokines. We report an adult recipient of an ex vivo expanded, HLA-mismatched, unrelated cord blood transplant who experienced a late extramedullary relapse while still in hematologic remission. Despite demonstrating immune tolerance on minimal immunosuppressive agents, a brief course of intravenous interleukin-2 resulted in rapid, aggressive graft-versus-host and graft-versus-leukemia reactions. This case highlights the potential of cytokine immunomodulation following cord blood transplantation, but also suggests caution in stimulating these cells.

Detection of a dormant 20q- leukemia clone in bone marrow cultures with hematopoietic growth factors: implications for secondary leukemia post-transplant.

A patient developed secondary acute myelogenous leukemia with a 20q- marker chromosome abnormality six years following chemotherapy and radiation for Hodgkins disease (HD). Routine cytogenetics on the bone marrow which had been harvested and cryopreserved immediately following completion of initial therapy for HD showed no cytogenetic abnormality. However, a 20q- clonal marker was detected after culturing bone marrow with hematopoietic growth factors (HGF). The marrow was used successfully for an autotransplant. Post-transplant, the 20q- marker was again detected in HGF cultured samples. The patient relapsed at 165 days post-transplant with the 20q- marker and trisomy 21. These data suggest that standard cytogenetic assays may not detect abnormal clones which can cause leukemia post-transplant.

Factors associated with response to platelet transfusion following hematopoietic stem cell transplantation.

We studied 526 consecutive post-transplant platelet transfusions to determine the factors associated with response to platelet transfusion in the BMT setting. Poor responses to platelet transfusions occurred frequently, with 310 of the 484 evaluable transfusions (64%) resulting in post-infusion corrected count increments of less than 7500. Factors associated with poor response to platelet transfusion by both univariate and multivariate analysis included, (1) presence of serum lymphocytotoxic antibodies; (2) male sex; (3) body surface area greater than 1.7 m2; (4) transfusion of red cells on the day of the platelet infusion; (5) concurrent administration of steroids; (6) major ABO mismatch between the recipient and the platelet product; and (7) (among women) a history of one or more pregnancies prior to transplant. Paradoxically, a history of greater than 25 blood product exposures prior to transplant, and evidence of prior CMV infection in either the bone marrow donor or recipient were associated with higher CCIs by both univariate and multivariate analysis. Factors that showed little correlation with response to platelet transfusion included, (1) age of the infused platelet product; (2) concurrent fever; (3) recent administration of intravenous immunoglobulin; and (4) absolute neutrophil count at the time of the infusion. The factors associated with response to platelet transfusion in BMT patients appear to be different from those observed in the non-transplant setting.