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Biomedical subjects

T G Gross

Publications and source records attributed to T G Gross.

At least 19 recordsLinked to original sources
PubMed2006

Liver transplantation for primary or metastatic sarcoma to the liver.

Sarcoma is generally a rare disease in the US, with poor survival in patients with both primary angiosarcoma and metastatic disease from sarcoma and GIST. In order to determine if liver transplantation for sarcoma is a realistic option, we examined records of all patients in the US component of the Israel Penn International Transplant Tumor Registry were reviewed. Those patients with liver failure from primary or metastatic liver sarcoma were evaluated. Patient outcome analysis was then performed. Patient and tumor demographics were reviewed as well as patient survival after transplantation. 19 patients are identified having received liver transplantation after treatment for sarcoma of the liver, 6 patients with primary hepatic sarcoma and 13 patients with metastatic sarcoma of the liver. Recurrence was almost universal in 18 of 19 patients (95%) after a median interval of 6 months. Survival for the group as a whole was 47% for 1-year, 15% for 3-years and 5% for 5-years. Given the early recurrence of tumor and meager 1-year survival outcome, liver transplantation is a poor therapeutic choice for patients with either primary or metastatic liver sarcoma, including high-grade leiomyosarcoma (GIST) regardless of primary site or primary therapy.

Adult↗
PubMed2005

Chemotherapy for posttransplant lymphoproliferative disorder: the Israel Penn International Transplant Tumor Registry experience.

INTRODUCTION: Very little published data exist regarding the results of chemotherapy treatment of posttransplant lymphoproliferative disorder (PTLD). The purpose of the study was to review the Israel Penn International Transplant Tumor Registry experience with PTLD treated with chemotherapy. METHODS: Patients with PTLD who received chemotherapy were identified and data collected regarding demographics, tumor characteristics, recurrence rates, and survival. RESULTS: One hundred ninety three solid organ transplant recipients with PTLD who received chemotherapy were identified. Most patients were male (142:51) and Caucasian (148; 16 AA, 29 unspecified). Most PTLD were B-cell predominant (81%), monoclonal (71), and CD 20+ (60% of patients tested). Organ transplanted included: kidney, 92 (48%); heart, 54 (28%); liver, 30 (16%); pancreas, 8 (4%); and lung, 9 (5%). Median time to presentation posttransplant was 24.5 months (range 0.8 to 226.5 months). Ninety patients received CHOP, 12 ProMACE, 65 other multidrug regimens, and 23 patients received single-agent chemotherapy. Five-year survival for these four regimens were: 24%, 25%, 32%, and 5%. PTLD-specific death rates were 34%, 34%, 40%, and 48%. CONCLUSIONS: Single-agent chemotherapy appears to be inferior to other chemotherapy regimens for PTLD as it is associated with lower survival.

Antigens, CD↗
PubMed2005

Prostate cancer prior to solid organ transplantation: the Israel Penn International Transplant Tumor Registry experience.

INTRODUCTION: Prostate adenocarcinoma (PCA) is the second leading cause of cancer-related deaths in men, and with routine prostrate specific antigen (PSA) screening, is being diagnosed with increasing frequency. To date, reported experiences with transplantation in men with a history of PCA are limited to only a few patients. This study presents the first series of transplant recipients with a history of PCA. METHODS: Analysis of transplant recipients with a history of pretransplant PCA was performed on the Israel Penn International Transplant Tumor Registry database. PCA were staged using American Joint Committee on Cancer criteria. Statistics analysis was performed by chi-square and Student t tests. RESULTS: Ninety patients with preexisting PCA were identified: 77 renal, 10 heart, and three liver transplant recipients. Mean age at PCA diagnosis was 61.3 +/- 6.3 years. Median interval between diagnosis and transplantation was 19.3 months, and median follow-up after transplantation was 20.5 months. Median time to PCA recurrence was 10.6 months after transplantation and median survival time with recurrent PCA was 49.2 months after transplant. Patient mortality was 28.8%, and PCA-related death rate was 7.8%. PCA recurrence rate was 17.7%. Tumor recurrence rates in stage I and II disease (14 and 16%) were lower than in stage III disease (36%). CONCLUSIONS: In conclusion, death rate to disease other than PCA is three times that due to PCA. PCA recurrence rates are relatively low in patients who initially presented with stage I and II disease, and are half that of patients with stage III disease.

Adenocarcinoma↗
PubMed2005

Posttransplant lymphoproliferative disorder: significance of central nervous system involvement.

BACKGROUND: Few data exist regarding central nervous system (CNS) involvement in patients with posttransplant lymphoproliferative disorder (PTLD). The purpose of this study was to review the Israel Penn International Transplant Tumor Registry (IPITTR) experience with CNS involvement by PTLD. METHODS: Nine hundred ten PTLD cases from the United States were reported to the IPITTR and reviewed for CNS involvement. RESULTS: One hundred thirty-six transplant recipients with PTLD (15%) had CNS involvement. The highest incidence of CNS involvement occurred in pancreas (3 of 11; 27%) and kidney transplant recipients (76 of 429; 18%). Fifteen cases occurred in children and 121 cases in adults. For both children and adults, isolated CNS disease was associated with better survival when compared with multiple-site involvement (children: 29% vs 0%; adults: 12% vs 6%; P < .05). Three-year survival in PTLD patients with CNS involvement was 9.4% and without CNS involvement was 49.4% (P < .01). Radiation therapy alone appeared to provide the best survival rates (25%). CONCLUSIONS: CNS involvement in transplant recipients with PTLD carries an ominous prognosis; however, isolated CNS involvement has a better prognosis than CNS plus extracranial involvement. Radiation therapy alone provides the best results, but this may be a reflection of isolated CNS disease.

Adult↗
PubMed2005

Allogeneic stem cell transplantation in X-linked lymphoproliferative disease: two cases in one family and review of the literature.

X-linked lymphoproliferative disease (XLP) is a rare immunodeficiency caused by mutations in the signaling lymphocyte activating molecule-associated protein/SH2D1A gene and characterized by a dysregulated immune response to Epstein-Barr virus and other pathogens. The clinical presentation is heterogeneous and includes fulminant infectious mononucleosis, lymphoma, hypogammaglobulinemia and aplastic anemia. XLP is associated with a high morbidity and overall outcome is poor. At present, allogeneic stem cell transplantation (alloSCT) is the only curative treatment. XLP patients may be recognized in various stages of disease and even when symptoms are not yet evident. We here present two related XLP patients in different stages of disease that were both treated successfully with alloSCT using a matched unrelated donor. In addition, we have reviewed all reported cases of alloSCTs in XLP patients. Based on these results and in order to improve the final outcome, we conclude that alloSCT should be recommended in both symptomatic and asymptomatic XLP patients.

Child↗
PubMed2001

Pediatric hematopoietic stem cell transplantation.

The successful use of allogeneic HSCT for children with malignant and nonmalignant diseases continues to be limited by the development of acute and chronic GVHD, infectious complications, delayed recovery of the immune system, acute and long-term toxicity, and relapse of disease. Significant advances have been made, particularly in the ability to identify suitable sources of HSC. Future advances will depend on a better understanding of the biology of HSC sources, GVHD, immune reconstitution, and common complications. Improved therapies are dependent on participation of children in well-designed, translational and clinical transplant studies.

Antibodies, Monoclonal↗
PubMed2000

Correlation of mutations of the SH2D1A gene and epstein-barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease.

The purposes of this study were to determine the frequency of mutations in SH2D1A in X-linked lymphoproliferative disease (XLP) and the role of SH2D1A mutations and Epstein-Barr virus (EBV) infection in determining the phenotype and outcome of patients with XLP. Analysis of 35 families from the XLP Registry revealed 28 different mutations in 34 families-large genomic deletions (n = 3), small intragenic deletions (n = 10), splice-site (n = 3), nonsense (n = 3), and missense (n = 9) mutations. No mutations were found in 25 males, so-called sporadic XLP (males with an XLP phenotype after EBV infection but no family history of XLP) or in 9 patients with chronic active EBV syndrome. Of 304 symptomatic males in the XLP Registry, 38 had no evidence of EBV infection at first clinical manifestation. When fulminant infectious mononucleosis (FIM) was excluded, there was no statistical difference in the frequency of EBV infectivity in the other XLP phenotypes. Furthermore, there was no difference at age of first clinical manifestation between EBV(+) and EBV(-) males or in survival when patients with FIM were excluded. In conclusion, it was found that mutations in the SH2D1A gene are responsible for XLP but that there is no correlation between genotype and phenotype or outcome. It was also found that though EBV infection often results in FIM, it is unnecessary for the expression of other manifestations of XLP, and it correlates poorly with outcome. These results suggest that unidentified factors, either environmental or genetic (eg, modifier genes), contribute to the pathogenesis of XLP.

Alternative Splicing↗
PubMed2000

A review of Epstein-Barr virus infection in patients with immunodeficiency disorders.

Epstein-Barr virus (EBV), one of 8 known human herpesviruses, infects the vast majority of mankind and infections are generally subclinical. However, EBV infection has been associated with a spectrum of diseases, lymphoproliferative diseases (EBV-LPD) in particular, including malignant lymphoma. EBV-LPD are frequently observed in patients with primary or secondary immunodeficiencies. The incidence of EBV-LPD is on the rise, partly because of increasing numbers and success of hematopoietic stem cell and solid organ transplants and partly because many patients with immunodeficiencies, both primary and secondary, including AIDS, live longer, with improvements in supportive care. Herein, a spectrum of EBV-associated diseases in patients with immunodeficiency are summarized and discussed mainly focusing on their pathogenetic mechanism(s).

Acquired Immunodeficiency Syndrome↗
PubMed1999

Cyclosphosphamide/prednisone for combination immunosuppression and therapy of lymphoproliferative disease.

Post-transplant lymphoproliferative disease (PTLD) is a well-known complication of solid organ transplantation. While this disorder can often be controlled by decreasing immunosuppression, it is frequently difficult to control the resultant rejection. This case exemplifies this dilemma. To solve this problem, cyclosphosphamide (600 mg/m2) and prednisone (2 mg/kg times 5 days) were given every 3 weeks to simultaneously treat PTLD and provide immunosuppression.

Cyclophosphamide↗
PubMed1999

B cell lymphoproliferative disorders following hematopoietic stem cell transplantation: risk factors, treatment and outcome.

Twenty-six cases of B cell lymphoproliferative disorder (BLPD) were identified among 2395 patients following hematopoietic stem cell transplants (HSCT) for which an overall incidence of BLPD was 1.2%. The true incidence was probably higher, since 9/26 of the diagnoses were made at autopsy. No BLPD was observed following autologous HSCT, so risk factor analyses were confined to the 1542 allogeneic HSCT. Factors assessed were HLA-mismatching (> or = 1 antigen), T cell depletion (TCD), presence of acute GvHD (grades II-IV), donor type (related vs unrelated), age of recipient and donor, and underlying disease. Factors found to be statistically significant included patients transplanted for immune deficiency and CML, donor age > or = 18 years, TCD, and HLA-mismatching, with recipients of combined TCD and HLA-mismatched grafts having the highest incidence. Factors found to be statistically significant in a multiple regression analysis were TCD, donor age and immune deficiency, although 7/8 of the patients with immunodeficiencies and BLPD received a TCD graft from a haploidentical parent. The overall mortality was 92% (24/26). One patient had a spontaneous remission, but subsequently died >1 year later of chronic GVHD. Thirteen patients received therapy for BLPD. Three patients received lymphocyte infusions without response. The only patients with responses and longterm survival received alpha interferon (alphaIFN). Of seven patients treated with alphaIFN there were four responses (one partial and three complete). These data demonstrate that alphaIFN can be an effective agent against BLPD following HSCT, if a timely diagnosis is made.

Acyclovir↗
PubMed1999

Autologous hematopoietic stem-cell transplantation for relapsed or refractory Hodgkin's disease in children and adolescents.

PURPOSE: To determine the treatment outcome and clinical factors that are of prognostic significance for children and adolescents with relapsed or refractory Hodgkin's disease (HD) who received treatment with high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: Fifty-three consecutive children and adolescents 21 years of age or younger with relapsed or refractory HD underwent HSCT. RESULTS: At day 100 after transplantation, 29 patients (55%) were in a complete remission or maintained a continuous complete response, six (11%) had a partial response, and 11 (21%) failed to respond or had progressive disease. The failure-free survival (FFS) at 5 years was 31%, and overall survival was 43%. Twenty-one patients died of progressive HD, and nine died secondary to transplantation-related complications, including two secondary leukemias. Prognostic factors important for FFS were normal pretransplantation lactate dehydrogenase levels (5-year FFS = 42%), compared with patients with elevated LDH levels (5-year FFS = 0%) (P < .001), and disease sensitivity at the time of HSCT with FFS in untreated relapse, sensitive disease, and resistant disease 44%, 35%, and 9%, respectively (P = .06). There was no statistically significant difference in FFS or overall survival between age subgroups that were analyzed (< 13, 13 to 18, 19 to 21) or in comparison with an adult cohort. CONCLUSION: HSCT is an effective treatment modality that can result in long-term cures and should be considered for children and adolescents with relapsed HD.

Adolescent↗
PubMed1998

Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies.

Forty-one patients were studied at set times after allogeneic blood stem cell transplantation (alloBSCT) for recovery of lymphocyte numbers and function. Cells were mobilized with G-CSF from HLA-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate; G-CSF was administered post-transplant. Median time to absolute lymphocyte count (ALC) >500/microl was 17 days vs 41 and 49 days in historical alloBMT patients with G-CSF (n = 23) or no cytokine (n = 29) post-transplant, respectively (P < 0.0001). CD4/CD8+ ratio was 1.9 on day 28 after alloBSCT, then gradually declined to 0.8 at 1 year due to more rapid CD8+ cell recovery. Mean phytohemagglutinin-induced T cell responses were lower than normal on day +28 (P < 0.05), then tended to recover towards normal values. Natural-killer cytotoxicity remained low from day +28 to 1 year post-alloBSCT, but considerable lymphokine-activated killer cytotoxicity was induced from cells already obtained on day +28. Faster lymphocyte recovery correlated with better survival in alloBSCT patients (median follow-up 287 days, P = 0.002), ALC recovery was not affected by acute GVHD, CMV infections or doses of infused cells. ALC recovery did not correlate with survival in either historical alloBMT group. These data suggest that after alloBSCT lymphocyte reconstitution is faster than after alloBMT, and that quicker lymphocyte recovery predicts better survival in the alloBSCT setting.

Adult↗
PubMed1998

Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells.

Although the hematopoietic reconstituting ability of human umbilical cord blood cells (UCBC) is well documented, their antitumor cytotoxic potential has not been well studied. Therefore, UCBC were compared to normal peripheral blood stem cells (PBSC) and bone marrow (BM) stem cell harvests for cytomorphology, antitumor cytotoxic activity before and after ex vivo cytokine manipulation, response to T and B cell mitogens, expression of adhesion molecules and immunophenotypes using flow cytometry, cytokine production and in vivo antitumor activity. BM and PBSC, but not UCBC, did not form cellular clusters in culture. More cytotoxic granules were present in the cytoplasm of UCBC than PBSC following activation in vitro. Ex vivo manipulation of UCBC with cytokines produced more cytotoxicity to K562 and Raji tumor cells than PBSC or BM (p<0.001). Most cytotoxic cells in UCBC cultures were T lymphocytes, and a correlation existed between the number of CD56+ cells and cytotoxicity levels, particularly after in vitro activation with interleukin-2. No significant difference in adhesion molecule expression was noted among UCBC, PBSC and BM cells. However, there was a significantly decreased expression of CD54 molecules (ICAM) on UCBC compared to PBSC (p<0.05). IL-2 activated UCBC showed significant antitumor effects against K562 leukemic cells grown in SCID mice. Thus UCBC contained more antitumor effector cells and precursors than cells from marrow or peripheral blood cells which might be capable of providing a therapeutic effect.

Animals↗
PubMed1998

Depletion of EBV-infected cells in donor marrow by counterflow elutriation.

Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disease (PTLD) is a well-recognized complication of T cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). Certain methods of TCD, such as counterflow elutriation (CE), have not been associated with an increased incidence of PTLD. Since CE depletes B cells as well as T cells, the hypothesis that CE depletes donor marrow of EBV-infected cells was tested in this study. Marrow samples from 70 donors were assayed by qualitative and semi-quantitative polymerase chain reaction (PCR) amplification to detect EBV DNA in four cellular fractions produced by elutriation: a small cell fraction (F70), two intermediate-sized cell fractions (F110 and F140), and a large cell (hematopoietic precursor-enriched, lymphocyte-depleted) rotor-off (R/O) fraction. The distribution of B cells in elutriation fractions was 21% (F70), 59% (F110), 18% (F140), and 2% (R/O). Qualitatively, the frequency of EBV DNA detected in fractions was 49% (F70), 57% (F110), 73% (F140), and 44% (R/O). The relative concentration of EBV DNA in each fraction was determined by semiquantitative PCR. The mean number of EBV DNA copies per 150,000 cells was 0.57 (F70), 4.6 (F110), 5.7 (F140), and 0.61 (R/O). Relative EBV DNA load in each fraction was calculated by multiplying the mean concentration of EBV DNA per fraction and mean mononuclear cell content in each fraction. The relative distribution of EBV DNA was 0.5, 58, 40, and 1.5% in the F70, F110, F140, and R/O fractions, respectively. No correlation between the amount of EBV in the graft and development of PTLD could be made, because only one of the 70 recipients developed PTLD and this was following autologous hematopoietic recovery. Although these results demonstrate that the majority of EBV-infected cells in marrow are separated from the TCD graft by counterflow elutriation, further studies are required to differentiate the role of this phenomenon from that of other potential factors, such as the amount of T cell depletion and recovery of EBV immunity in the pathogenesis of PTLD after BMT.

Bone Marrow Cells↗