[Role of stem cell transplantation in treatment of primary cutaneous T­cell lymphoma]. / Stellenwert der Stammzelltransplantation in der Therapie kutaner T­Zell-Lymphome.

BACKGROUND: Within the heterogeneous group of cutaneous T­cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. OBJECTIVE: The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. MATERIAL AND METHODS: A literature search using the keywords "hematopoietic stem cell transplantation" and "cutaneous T­cell lymphoma" was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. RESULTS: After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. CONCLUSION: Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T­cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision.

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 (75 %). On average, the patients were diagnosed 6 years (range 2-12) prior to transplant with an average of 4 years (range 1-8) from time of first-line therapy to transplant. The remission states at the time of transplant were complete remission (CR) (n = 4), stable disease (n = 10), partial remission (n = 20) and progressive disease (n = 6). Only reduced intensity conditioning regimens were employed. The average CD34(+) cell dose was 4.16 × 10(6)/kg. Neutrophil engraftment was seen by day +17 (range 10-23) post-transplant, and 88 % achieved 95-100 % donor chimerism by day 100. Overall survival, progression-free survival and non-relapse mortality at 2 years post-transplant were 65, 52.5 and 27.5 %, respectively. A total of 51 % of patients were found to be minimal residual disease (MRD)-negative at 1 year 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.

Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial.

Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P<0.0001). Risk-adapted, treosulfan-based therapy with auto- and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation.

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.

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.

Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program.

The CXCR4-inhibitor plerixafor mobilizes hematopoietic stem cells amplifying the effects of granulocyte-CSF (G-CSF). Before approval plerixafor was used in a compassionate use program (CUP) for patients who failed a previous mobilization. In the German CUP 60 patients from 23 centers (median age 56.5 years (2-75)) were given 240 µg/kg plerixafor SC 9-11 h before apheresis. A total of 78.3% (47/60) received G-CSF for 4 days before plerixafor administration; 76.6% of those (36/47) yielded at least 2.0 × 10(6) CD34(+) cells/µL. The median cell yield was 3.35 × 10(6) CD34+ cells/kg (0-29.53). Nine patients received plerixafor alone or with G-CSF for less than 4 days mobilizing a median of 3.30 × 10(6) CD34+ cells/kg (1.6-5.6). There was no significant difference between G-CSF application for 4 days and for a shorter period of time (P=0.157). A total of 47 patients received plerixafor plus G-CSF combined with chemotherapy yielding a median of 3.28 × 10(6) CD34+ cells/kg (0-24.79). In all, 40 of 60 patients (66.7%) proceeded to transplantation, and achieved a timely and stable engraftment. Side effects were rare and manageable. In conclusion, mobilization with plerixafor in poor mobilizers is safe and results in a sufficient stem cell harvest in the majority of patients.

Human herpesvirus-6 as an inducer of porphyria cutanea tarda: implications from a case.

Here we describe a case that might deliver a link between sporadic porphyria cutanea tarda (PCT) and human-herpesvirus-6 (HHV6) hepatitis. Sporadic PCT is a rare disease of the heme synthesis pathway. The pathogenesis has not been fully determined but iron overload and viral infections - e.g., hepatitis C virus - are thought to play an important role. We present the case of a patient suffering from myelo-monocytic leukemia. He developed symptomatic sporadic PCT concomitant with HHV6-associated subclinical hepatitis after allogeneic stem cell transplantation (SCT). Although HHV6 often reactivates after SCT and HHV6-induced hepatitis can occur in immunocompromised patients, it has not been described that HHV6 might trigger PCT. A contribution of HHV6 to the pathogenesis of sporadic PCT could have dramatic implications on our current therapeutic approach.