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Context.--In the early 1980s, a monoclonal antibody termed Ki-1 was developed against a cell line derived from a patient with Hodgkin lymphoma. This antibody detected a limited number of benign activated lymphocytes in lymphoid tissue, whereas in Hodgkin lymphoma it appeared to be nearly specific for Reed-Sternberg cells and their mononuclear variants. Subsequent studies showed that Ki-1 expression defined a new type of lymphoma that was later designated anaplastic large cell lymphoma with or without anaplastic large cell kinase expression/translocation. In the past 30 years, numerous new lymphoma entities have been defined, many of which are variably positive for CD30. Many virally transformed lymphoproliferative disorders are also frequently positive for CD30. Objective.--To illustrate the broad spectrum of [CD30.sup.+] hematologic malignancies and to provide an update of CD30-targeted therapies. Data Sources.--Personal experiences and published works in PubMed. Conclusions.--Because of its low expression in normal tissue, CD30 was studied as a therapeutic target for many years. However, the first functional humanized antibody against CD30 was developed only about 10 years ago. Brentuximab vedotin is a humanized anti-CD30 antibody linked to a cytotoxin, and was approved by the US Food and Drug Administration in 2012 for treating refractory Hodgkin lymphoma and anaplastic large cell lymphoma. Since then, the list of Food and Drug Administration-approved CD30-targeted hematologic malignancies has grown. Recently, the therapies using tumor antigen-specific chimeric antigen receptor T cells targeting CD30 have incited a great deal of enthusiasm and are studied in clinical trials., This review focuses on clinicopathologic features and treatments of selective [CD30.sup.+] lymphoproliferative disorders. Quite a number of hematologic malignancies are either defined or characterized by the expression of CD30. More [...]

BACKGROUND. Adoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications. METHODS. We provide results of a personalized T cell manufacturing program evaluating donor, patient, T cell product, and outcome data. Patient-tailored clinical-grade EBV-specific cytotoxic T lymphocyte (EBV-CTL) products from stem cell donors (SCDs), related third-party donors (TPDs), or unrelated TPDs from the allogeneic T cell donor registry (alloCELL) at Hannover Medical School were manufactured by immunomagnetic selection using a CliniMACS Plus or Prodigy device and the EBV PepTivators EBNA-1 and Select. Consecutive manufacturing processes were evaluated, and patient outcome and side effects were retrieved by retrospective chart analysis. RESULTS. Forty clinical-grade EBV-CTL products from SCDs, related TPDs, or unrelated TPDs were generated for 37 patients with refractory EBV infections or EBV-associated malignancies with and without a history of transplantation, within 5 days (median) after donor identification. Thirty-four patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to a complete response in 20 of 29 patients who were evaluated for clinical response. No infusion-related toxicity was reported. EBV-specific T cells in patients' blood were detectable in 16 of 18 monitored patients (89%) after transfer, and their presence correlated with clinical response. CONCLUSION. Personalized clinical-grade manufacture of EBV-CTL products via immunomagnetic selection from SCDs, related TPDs, or unrelated TPDs in a timely manner is feasible. Overall, EBV-CTLs were clinically effective and well tolerated. Our data suggest EBV-CTL transfer as a promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT, as well as patients with preexisting organ dysfunction. TRIAL REGISTRATION. Not applicable. FUNDING. This study was funded in part by the German Research Foundation (DFG, 158989968/SFB 900), the Deutsche Kinderkrebsstiftung (DKS 2013.09), Wilhelm-Sander-Stiftung (reference 2015.097.1), Ellen-Schmidt-Program of Hannover Medical School, and German Federal Ministry of Education and Research (reference 01E00802)., Introduction Morbidity and mortality in patients with hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) are frequently caused by graft rejection or graft-versus-host disease (GvHD) and increased by [...]

The fatal immune dysregulation that sometimes follows EBV infection in boys has been linked to mutations in two X chromosome--encoded genes, SLAM-associated protein (SAP) and X-linked inhibitor of apoptosis (XIAP). In this study we describe 2 girls from a consanguineous Turkish family who died after developing severe immune dysregulation and therapy-resistant EBV-positive B cell proliferation following EBV infection. SNP array--based genome-wide linkage analysis revealed IL-2-inducible T cell kinase (ITK) as a candidate gene for this immunodeficiency syndrome. Both girls harbored a homozygous missense mutation that led to substitution of a highly conserved residue (R335W) in the SH2 domain of ITK. Characteristics of ITK deficiency in mouse models, such as absence of NKT cells and high levels of eomesodermin in [CD8.sup.+] cells, were seen in either one or both of the girls. Two lines of evidence suggested that R335W caused instability of the ITK protein. First, in silico modeling of the mutant protein predicted destabilization of the SH2 domain. Additionally, Western blot analysis revealed that, unlike wild-type ITK, the R335W mutant was nearly undetectable when expressed in 293 T cells. Our results suggest that ITK deficiency causes what we believe to be a novel immunodeficiency syndrome that leads to a fatal inadequate immune response to EBV. Because ITK deficiency resembles EBV-associated lymphoproliferative disorders in boys, we suggest that this molecular cause should be considered during diagnosis and treatment., Introduction Severe immune dysregulation in boys after primary infection with EBV, presenting as fatal mononucleosis, hemophagocytosis, hypogammaglobulinemia, and lymphoproliferation, is the hallmark of X-linked lymphoproliferative disease (XLP), a well-known inherited [...]

The expanding armamentarium of biologic agents, phototheraputic and irradiation techniques and combination regimens available to treat mycosis fungoides is discussed.

Abstract Cutaneous T-cell lymphomas (CTCLs) are a relatively uncommon group of lymphoproliferative disorders in which a malignant population of T cells is localized to the skin at presentation. Of the [...]

Byline: A. Swiatecka-Urban (1), Clotilde Garcia (2), Dianne Feuerstein (3), Samuel Suzuki (4), Prasad Devarajan (2), Richard Schechner (3), Stuart Greenstein (3), Vivian Tellis (3), Frederick Kaskel (2) Keywords: Keywords Basiliximab; Tacrolimus; Target levels; Post-transplant lymphoproliferative disease; Post-transplant diabetes mellitus Abstract: Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with a$?3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels. Author Affiliation: (1) Ira Greifer Pediatric Kidney Center, 3326 Bainbridge Avenue, Bronx, NY 10467, USA. ajaswurban001@worldnet.att.net, US (2) Department of Pediatrics, Division of Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA, US (3) Department of Surgery, Division of Transplantation, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA, US (4) Department of Biomedical Statistics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA, US Article note: Received: 19 December 2000 / Revised: 23 April 2001 / Accepted: 24 April 2001

Infusions of unirradiated donor leukocytes may be an effective treatment for Epstein-Barr virus (EBV)-associated lymphoproliferative disease after allogeneic bone marrow transplantation. EBV-associated lymphoproliferative disorders occur in marrow-transplant recipients, resulting in malignant B-cell lymphomas that can be fatal. EBV-associated lymphoproliferative disorders were successfully eradicated in five marrow transplant recipients through the infusion of unirradiated leukocytes from the marrow donors. Two of these patients had monoclonal proliferations of the disorder, the type that is usually fatal. Two of the patients died from causes believed to be unrelated to the donor leukocyte treatment, but autopsies revealed that the leukocyte treatment had successfully lessened the tumors associated with EBV-associated lymphoproliferative disease. The three surviving patients showed recovery from the EBV-associated lymphoproliferative disease, with graft-versus-host disease being the only possible side effect noted.

Abstract CD30+ cutaneous lymphoproliferative disorders, the second most common cutaneous T-cell lymphoma after mycosis fungoides, represent a spectrum of conditions ranging from lymphomatoid papulosis to borderline CD30+ lesions to anaplastic [...]

By formal definition, a protocol is the description of steps to be taken in an experiment. In its simplest sense, that is what the CALGB 9251 protocol is. The Cancer [...]

Context.--Posttransplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations occurring in the setting of solid organ or bone marrow transplantation. They show a clinical, morphologic, and molecular genetic spectrum ranging from reactive polyclonal lesions to frank lymphomas. The close association with Epstein-Barr virus has been established and the pathogenetic role of this virus is becoming better understood. Although they are relatively uncommon, PTLDs are a significant cause of morbidity and mortality in transplant patients. Objective.--To review the incidence, risk factors, clinical features, pathogenesis, and classification of PTLDs. Data Sources.--We reviewed relevant articles indexed in PubMed (National Library of Medicine), with emphasis on more recent studies. The classification of PTLDs is based on the most current World Health Organization classification text. Conclusions.--Posttransplantation lymphoproliferative disorders are a heterogeneous group of disorders showing a wide clinical and morphologic spectrum. Although relatively uncommon, PTLDs represent a serious complication after transplantation. Many risk factors for PTLD are well established, including transplanted organ, age at transplant, and Epstein-Barr virus seronegativity at transplant. However, other factors have been implicated and still require additional examination. Recent studies are shedding some light on the pathogenesis of PTLDs and defining relevant pathways related to Epstein-Barr virus. As the pathogenesis of PTLDs is further elucidated, the classification of PTLDs will most likely evolve. (Arch Pathol Lab Med. 2007;131:1209-1218), Posttransplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations occurring in the setting of solid organ or bone marrow transplantation. It has long been known that intact immune [...]

Abstract This is a report of a case of Epstein-Barr virus (EBV) associated haemophagocytic syndrome in a 17 year old woman with antibody deficiency. For two years before this presentation, [...]

Introduction: Survival of children with lymphoproliferative disease (LPD) still remains poor, particularly in non-post transplant lymphoproliferative disease (PTLD) cases. Anti CD20 (rituximab), a highly specific mouse/human chimaeric antibody, has shown [...]