S. Theurich

Allogeneic stem cell transplantation for advanced primary cutaneous T-cell lymphoma: a systematic review.

Primary cutaneous T-cell lymphomas (CTCL) are non-Hodgkin lymphomas usually running an indolent course. However, some patients progress to tumor stages or leukemic phase for which no curative treatment is available. Although initial response rates are high, remissions are often short-lived. Recent reports suggest a potential curative role for allogeneic stem cell transplantation (alloSCT). We searched databases for genetically randomized controlled trials (RCT) comparing alloSCT with conventional therapy. Data extraction and quality assessment were performed following the guidelines of the Cochrane Collaboration. Primary outcome measures were overall survival, secondary criteria included time-to-progression and response rate. A total number of 2077 primary citations were screened for relevant studies. Detailed analysis revealed that no RCTs on this subject have been performed and no systematic meta-analysis could be carried out. Nevertheless, several retrospective analyses and case series addressed the question of alloSCT for patients with advanced CTCL or Sézary syndrome. In this review, we will discuss the currently available data.

Hypoxia-induced p38 MAPK activation reduces Mcl-1 expression and facilitates sensitivity towards BH3 mimetics in chronic lymphocytic leukemia

Hypoxia-induced p38 MAPK activation reduces Mcl-1 expression and facilitates sensitivity towards BH3 mimetics in chronic lymphocytic leukemia

CD30-targeted therapy with brentuximab vedotin and DLI in a patient with T-cell posttransplantation lymphoma: induction of clinical remission and cellular immunity.

Posttransplantation lymphoproliferative disorder (PTLD) is a major complication after organ or allogeneic hematopoietic stem cell transplantation (alloSCT) (1). More than 90% of PTLD arise from B cells and are often associated with Epstein-Barr virus (EBV). Here, rituximab-containing treatment regimens have improved outcomes (2). T-cell PTLD constitutes a rare subgroup (2%Y6%) with a poor prognosis resulting in a median, subtype-dependent survival of 5 to 18 months (3, 4). Although 36% of the published T-cell PTLD patients were EBV positive, the exact pathomechanisms are still unclear and a number of other viruses have been associated with this condition (e.g., cytomegalovirus, human herpes virus, and human T lymphotropic virus) (4). In contrast to T-cell lymphoma in HIV-infected patients of which 18% to 28% show a CD30 anaplastic largecell phenotype, the expression of CD30 in T-cell PTLD has only been occasionally

Donor lymphocyte infusions combined with systemic PUVA/bexarotene as an effective bimodal immunologic approach in a patient with relapsed cutaneous T cell lymphoma after allogeneic stem cell transplantation.

One central challenge of allogeneic stem cell transplantation is the positive correlation between graft versus lymphoma effect (GvL) and graft-versus-host disease (GvHD). To date, specific targeting of GvL antigens with effector T cells and of GvHD antigens with specific regulatory T cells remains the subject of experimental research. In clinical reality, negative modulation of GvHD, e.g. by immunosuppression, reduces GvL and positive modulation of GvL, e.g. by donor lymphocyte infusions, often amplifies GvHD. Clinically feasible strategies to induce GvL while simultaneously reducing GvHD are urgently needed. Here, we report the case of an early relapsed primary cutaneous T cell lymphoma in tumor stage after allogeneic stem cell transplantation which was successfully treated with a parallel administration of donor lymphocyte infusions (DLI) and systemic PUVA and bexarotene which led to sustained complete remission without onset of acute GvHD. After termination of the treatment with PUVA/bexarotene subacute chronic GvHD occurred but was subsequently brought under control by extracorporeal photopheresis. We suggest that the combination of DLI and PUVA/bexarotene might be an interesting immunologic bimodal treatment option which warrants further investigation.

Cancer chemotherapy agents target intratumoral dendritic cells to potentiate antitumor immunity.

Cytotoxic drugs capable of killing cancer cells in conjunction with targeted conversion of tumor resident, tolerogenic dendritic cells (DCs) into efficient antigen presenting cells (APCs) are highly complementary therapeutic routes to boost antitumor immunity. Our data suggest that the microtubule-depolymerizing compounds Dolastatin 10 and Ansamitocin P3 may serve as prototypes for a class of agents that display this binary mode of action.

Short review of potential synergies of immune checkpoint inhibition and radiotherapy with a focus on Hodgkin lymphoma: radio-immunotherapy opens new doors

Radiotherapy is an established local treatment in patients with various malignancies. Systemic responses following local irradiation have been described as abscopal effects. Modern cancer immunotherapy with immune checkpoint inhibitors has shown impressive response rates and prolongation of survival even in heavily pretreated patients with advanced solid malignancies and lymphomas. Radiotherapy has been shown to modulate immune response, and its application in the context of immune checkpoint inhibition has recently evolved into an active field of research. Prospective studies investigating combination treatment are currently ongoing and will answer questions as to the optimal schedule and radiation dosing. This short review focuses on the immunomodulatory role of radiotherapy and the use of immune checkpoint inhibition with a special focus on Hodgkin lymphoma.

Nonmyeloablative allogeneic stem cell transplantation for chronic lymphocytic leukaemia offers the possibility of disease control with minimal morbidity and mortality--a single institution experience.

Allogeneic stem cell transplantation is a treatment option for patients with poor risk CLL. We conducted a retrospective analysis of all CLL patients allografted at our institution, the University Hospital of Cologne, Germany. Data was collected on 40 patients from 2004 to 2012. The mean age was 54, and the majority were male (75xa0%). On average, the patients were diagnosed 6xa0years (range 2–12) prior to transplant with an average of 4xa0years (range 1–8) from time of first-line therapy to transplant. The remission states at the time of transplant were complete remission (CR) (nu2009=u20094), stable disease (nu2009=u200910), partial remission (nu2009=u200920) and progressive disease (nu2009=u20096). Only reduced intensity conditioning regimens were employed. The average CD34+ cell dose was 4.16u2009×u2009106/kg. Neutrophil engraftment was seen by day +17 (range 10–23) post-transplant, and 88xa0% achieved 95–100xa0% donor chimerism by day 100. Overall survival, progression-free survival and non-relapse mortality at 2xa0years post-transplant were 65, 52.5 and 27.5xa0%, respectively. A total of 51xa0% of patients were found to be minimal residual disease (MRD)-negative at 1xa0year post-transplant. Our single-centre experience confirms the valuable role of allogeneic stem cell transplantation (allo-SCT) in the treatment of poor risk CLL patients with promising long-term survival and acceptable transplant-related mortality. The advent of newer therapeutic agents should not hinder the consideration of allo-SCT for this patient cohort as it remains the only curative option for these patients.