[Primary cutaneous lymphoma-a case series of 163 patients]. / Primär kutane Lymphome ­ eine Fallserie von 163 Patienten.

BACKGROUND: In addition to a broad and clinically diverse spectrum of known primary cutaneous lymphomas, for which an incidence of 1-3:100,000 is postulated, each year further entities are specified and defined. The goal is the presentation of a case series from daily clinical routine. METHODS: Over a period of 6 years and 2 months, patients consulting the Department of Dermatology, Medical Center University of Freiburg, were registered. Subsequently, collectives of mycosis fungoides (MF), Sezary syndrome (SS), CD30+ lymphoproliferative diseases, single cases with rare primary cutaneous lymphomas, and subcollectives of B­cell lymphomas were examined. The high number of MF cases allowed the additional quantitative analyses of the types of therapies used in this group. RESULTS: Yearly 16-25 new diagnoses of primary cutaneous lymphoma are made. The evaluation of 163 primary cutaneous lymphoma revealed 111 cases with MF (68.1%), including 9 particular variants, 15 primary cutaneous CD30+ lymphoproliferative diseases (9.2%) dominated by 10 lymphomatoid papulosis (LyP), in addition to 5 primary cutaneous anaplastic large cell lymphoma (PCALCL), 6 SS (3.68%), and 24 cutaneous B­cell lymphomas (14-72%). Three cases with rare primary cutaneous T/NK cell lymphomas are addressed in detail. In all, 82% of MF cases were stage IA and IB. The descending use of therapies for stage I-III included steroids and diverse UV therapies followed by bexarotene, interferon-α, methotrexate, and extracorporal photophoresis. CONCLUSIONS: Diagnoses of cutaneous lymphomas belong to a vast spectrum of differential diagnoses. This registry describes frequent findings and shows rare variants. You can only diagnose what you know; accordingly, a collection of case reports, which we wish to encourage, can help in processing and specification of entities.

Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency.

The gene PIK3CD codes for the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), and is expressed solely in leucocytes. Activating mutations of PIK3CD have been described to cause an autosomal dominant immunodeficiency that shares clinical features with common variable immunodeficiency (CVID). We screened a cohort of 669 molecularly undefined primary immunodeficiency patients for five reported mutations (four gain-of-function mutations in PIK3CD and a loss of function mutation in PIK3R1) using pyrosequencing. PIK3CD mutations were identified in three siblings diagnosed with CVID and two sporadic cases with a combined immunodeficiency (CID). The PIK3R1 mutation was not identified in the cohort. Our patients with activated PI3Kδ syndrome (APDS) showed a range of clinical and immunological findings, even within a single family, but shared a reduction in naive T cells. PIK3CD gain of function mutations are more likely to occur in patients with defective B and T cell responses and should be screened for in CVID and CID, but are less likely in patients with a pure B cell/hypogammaglobulinaemia phenotype.

Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans.

The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding TACI, in 13 individuals with common variable immunodeficiency. Homozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF. Family members heterozygous with respect to the C104R mutation and individuals with sporadic common variable immunodeficiency who were heterozygous with respect to the amino acid substitutions A181E, S194X and R202H had humoral immunodeficiency. Although signs of autoimmunity and lymphoproliferation are evident, the human phenotype differs from that of the Tnfrsf13b-/- mouse model.

Oncostatin M is a FIP1L1/PDGFRA-dependent mediator of cytokine production in chronic eosinophilic leukemia.

BACKGROUND: Chronic eosinophilic leukemia (CEL) is a myeloproliferative neoplasm characterized by expansion of neoplastic eosinophils, tissue infiltration, and organ damage. In a subset of these patients, the FIP1L1/PDGFRA (F/P) oncoprotein is detectable. F/P exhibits constitutive tyrosine kinase activity and activates a number of signaling pathways. So far, however, little is known about the role of F/P-dependent proteins in the pathogenesis of CEL. METHODS: A screen for F/P-dependent cytokines was performed in growth factor-dependent human cell lines lentivirally transduced with F/P. Signal transduction pathways were characterized in Ba/F3 cells with doxycycline-inducible expression of F/P and in EOL-1 cells. Cytokine expression was confirmed in patients' material by immunohistochemistry, immunofluorescence, and confocal microscopy. Gene expression analysis, proliferation assays, and chemotaxis assays were used to elucidate paracrine interactions between neoplastic eosinophils and stromal cells. RESULTS: We show that F/P upregulates expression of oncostatin M (OSM) in various cell line models in a STAT5-dependent manner. Correspondingly, neoplastic eosinophils in the bone marrow were found to overexpress OSM. OSM derived from F/P + cells stimulated proliferation of stromal cells. Moreover, OSM-containing supernatants from F/P + cells were found to upregulate production of stromal cell-derived factor-1 (SDF-1)/CXCL12 in human fibroblasts. SDF-1, in turn, induced migration of EOL-1 cells in a dose-dependent manner. CONCLUSIONS: We have identified a F/P-driven paracrine interaction between neoplastic eosinophils and stromal cells that may contribute to tissue fibrosis and accumulation of neoplastic eosinophils in CEL.

[Myelodysplastic syndromes. Epidemiology, molecular and morphological characteristics and risk stratification]. / Myelodysplastische Syndrome. Epidemiologie, molekulare und morphologische Merkmale, Risikostratifizierung.

Myelodysplastic syndromes (MDS) comprise a spectrum of clonal stem cell disorders which are currently defined according to the classification scheme of the revised 2008 WHO classification but which may be further refined in the future. The clinical presentation is often characterized by unexplained isolated or multiple peripheral blood cytopenias resulting in anemia, bleeding events or increased susceptibility to infections. The generally hypercellular, but rarely hypocellular and occasionally fibrotic bone marrow shows dysplastic features in ≥ 10 % of cells of at least one of the hematopoietic lineages. These features and enhanced apoptosis, stem cell senescence and immunologic dysregulation result in ineffective hematopoiesis. Diagnostics in MDS relies on complementary consideration of hematological, morphological and cytogenetic/molecular parameters. Methods include marrow and peripheral blood cytology, cytogenetics, fluorescence in situ hybridization (FISH), trephine bone marrow biopsy examination, immunophenotyping and the evaluation of molecular markers by established and new techniques. Mutations affecting growth factor receptors, cell cycle and apoptosis regulators, intracellular signaling, transcription factors, epigenetic regulation and the splicosome are involved in MDS pathogenesis and progression.

[Chronic myeloid neoplasms. Diagnostic criteria and current therapeutic concepts]. / Chronische myeloische Neoplasien. Diagnostische Kriterien und Ausblick auf aktuelle Theapiekonzepte.

Myeloproliferative neoplasms (MPNs) and related chronic disorders constitute a subgroup of myeloid malignancies which are defined according to clinical, morphological and molecular features by the actual World Health Organization classification of tumors of the haematopietic system. Screening procedures for a BCR-ABL fusion gene, JAK2, thrombopoietin receptor and KIT mutations are formally included in the diagnostic approach. Myelodysplastic/MPN overlap syndromes include rare entities such as refractory anemia with ringed sideroblasts characterized by a high proportion of JAK2V617F mutated cases. The paradigm of targeted treatment of chronic myeloid leukemia with imatinib has now been extended to eosinophilia-associated myeloid neoplasms with PDGFRA, PDGFRB or FGFR1 gene mutations. Pegylated interferon-alpha has convincingly been proved to reduce the JAK2 allele burden. JAK2 inhibitor drugs are currently being tested in clinical trials. The development of pathogenesis-targeted diagnostic and therapeutic approaches to the various MPNs will continue in the future.

Alternative implication of CXCR4 in JAK2/STAT3 activation in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive, rapidly metastasising tumour. Previously, we demonstrated the influence of CXCL12-CXCR4 interaction on processes involved in metastasis and chemoresistance in SCLC. We show here that STAT3 is expressed in both primary SCLC tumour tissues and SCLC cell lines. We investigated the function of STAT3 upon CXCL12 stimulation in SCLC cell lines. Small cell lung cancer cell lines present constitutive phosphorylation of STAT3, and in the reference cell lines NCI-H69 and NCI-H82 constitutive phosphorylation was further increased by CXCL12 stimulation. Further investigating this signalling cascade, we showed that it involves interactions between CXCR4 and JAK2 in both cell lines. However CXCL12-induced adhesion to VCAM-1 could be completely inhibited by the JAK2 inhibitor AG490 only in NCI-H82. Furthermore, CXCR4 antagonist but not AG490 inhibited cell adhesion whereas both antagonisms were shown to inhibit growth of the cells in soft agar, indicating the central involvement of this signalling in anchorage-independent growth of SCLC cells. Most interestingly, while using primary tumour material, we observed that in contrast to non-small-cell lung cancer samples from primary tumour tissues, all analysed samples from SCLC were strongly positive for tyrosine-phosphorylated STAT3. Taken together, these data indicate that STAT3 is constitutively phosphorylated in SCLC and is important in SCLC growth and spreading thus presenting an interesting target for therapy.

CD117 (c-kit) expression in human hepatocellular carcinoma.

AIMS: Although various methods of treatment have been tried, treatment options for advanced hepatocellular carcinoma (HCC) remain limited. Expression of the platelet-derived growth factor has been shown in HCC, which may derive from hepatic stem cells that express the c-kit proto-oncogene. Because of the promising results of imatinib and the key role played by c-kit in gastrointestinal stromal tumours and other solid tumours, the aim of this study was to determine the prevalence of c-kit (CD117) overexpression in patients with HCC. MATERIALS AND METHODS: A retrospective study of 258 archival specimens of subjects with histologically confirmed HCC was carried out. Expression of the c-kit proto-oncogene was evaluated by immunohistochemistry using rabbit anti-CD117 antibody A4502. RESULTS: The overall percentage of positive immunohistochemical staining of HCCs was 2.3% (6/258). CONCLUSIONS: Our results suggest that CD117 is not significantly overexpressed in HCC and there seems to be no role for the use of imatinib.

MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation.

Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a-/- dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected DCs ameliorated disease. Mechanistically, lack of miR-146a enhanced JAK2-STAT1 pathway activity, which led to higher expression of class II-transactivator (CIITA) and consecutively increased MHCII-levels on DCs. Inhibition of JAK1/2 or CIITA knockdown in DCs prevented miR-146a-/- DC-induced GVHD exacerbation. Consistent with our findings in mice, patients with the miR-146a polymorphism rs2910164 in hematopoietic cells displayed higher MHCII levels on monocytes, which could be targeted by JAK1/2 inhibition. Our findings indicate that the miR-146a polymorphism rs2910164 identifies patients at high risk for GVHD before allo-HCT. Functionally we show that miR-146a acts as a central regulator of recipient-type DC activation during GVHD by dampening the pro-inflammatory JAK-STAT/CIITA/MHCII axis, which provides a scientific rationale for early JAK1/2 inhibition in selected patients.

Bone marrow features improve prognostic efficiency in multivariate risk classification of chronic-phase Ph(1+) chronic myelogenous leukemia: a multicenter trial.

PURPOSE: Multivariate risk classifications for chronic (stable)-phase Ph(1+) chronic myelogenous leukemia (CML) are generally focused on hematologic variables, and the putative prognostic property of bone morphology has been neglected or even contested so far. PATIENTS AND METHODS: A total of 510 consecutively recruited patients in first chronic phase Ph(1+) CML and pretreatment bone marrow biopsy specimens were entered onto this multicenter observational trial to evaluate the effect of bone marrow histopathology. According to generally accepted criteria, patients with any signs of accelerated disease were excluded. Treatment modalities included administration of interferon alfa-2b (IFN) and chemotherapy with hydroxyurea (HU) or busulfan. Immunohistochemical and morphometric techniques were applied to identify marrow cells and to quantify fiber density. Patients were separated into learning and validation samples, and classification and regression tree (CART) analysis was performed to establish a prognostic decision tree. RESULTS: CART analysis of the validation sample (123 patients with HU therapy) revealed the amount of erythroid precursors in the bone marrow, myelofibrosis, and splenomegaly as the most important prognostic features. Three risk profiles with significantly different survival patterns were established, with median survival times ranging from 33 to 108 months (two-sided log-rank test, P =.0001). The new score was confirmed by application to the learning sample with IFN therapy (two-sided log-rank test, P =.0002). Furthermore, risk status defined by the new score was significantly correlated with the occurrence of blast transformation. CONCLUSION: Our data strongly implicate that prognostic classification of chronic-phase Ph(1+) CML can be significantly improved by the inclusion of morphologic parameters. The variables of the presented scoring system may be easily assessed by routinely processed aspirates and bone marrow trephines.

Complete remission of Crohn's disease after high-dose cyclophosphamide and autologous stem cell transplantation.

In a 36-year-old male with ileocolic Crohn's disease (CD) no long-lasting remission was obtained by treatment with corticosteroids, mesalazine, azathioprine and antibiotics. Surgical interventions due to relapsing fistulae and abscesses resulted in the removal of >1.5 m of small bowel and left only 40 cm of large bowel. In July 2000, a new fistula and abscess developed. The combination of corticosteroids, mesalazine, ciprofloxacin, metronidazol, azathioprine, formula diet and anti-TNF-alpha antibody largely reduced clinical activity, and resection of fistula and abscess were successful. Despite clinical remission, histology showed activity in the small bowel and the colon. In March 2001, stem cell mobilization chemotherapy with cyclophosphamide was performed. It induced an endoscopic remission for 9 months, which was maintained on azathioprine and corticosteroids. After relapse, in March 2002, high-dose chemotherapy with cyclophosphamide and reinfusion of T-cell-depleted autologous peripheral CD34+ blood stem cells were performed. This led to a complete clinical, endoscopical and histological remission for 9 months without any treatment. Thereafter, endoscopy showed initial aphthous lesions with minimal histological signs of inflammation. The patient is asymptomatic, but low-dose prednisolone and methotrexate are prophylactically given. Immunoablative chemotherapy followed by autologous peripheral blood stem cell transplantation may be a beneficial therapeutic option in complicated refractory CD.

Effects of chemotherapy (busulfan-hydroxyurea) and interferon-alfa on bone marrow morphologic features in chronic myelogenous leukemia. Histochemical and morphometric study on sequential trephine biopsy specimens with special emphasis on dynamic features.

We performed a retrospective clinicopathologic study on sequential biopsy specimens from 90 patients with Philadelphia chromosome-positive chronic myelogenous leukemia to study therapy-specific effects of busulfan (28 patients), hydroxyurea (32 patients), and interferon-alfa (IFN-alfa; 30 patients). Bone marrow specimens were evaluated by morphometry after silver impregnation and staining with monoclonal antibodies to identify reticulin fibers, nucleated erythroid precursors, megakaryocytes, and macrophages. To compute dynamics of histopathology implicating corresponding changes in time, relevant indices were calculated. Quantification of megakaryocytopoiesis and its precursor cell population showed a significant increase in the IFN-alfa and busulfan groups compared with the hydroxyurea group. These changes were associated with a development of myelofibrosis during therapy. Although a significant increase in fiber density was detectable in the busulfan group, the progression index proved to be twice as high after IFN-alfa therapy. In contrast, a considerable number of patients displayed a regression of myelofibrosis after hydroxyurea treatment. The general association of the megakaryocyte lineage with myelofibrosis was in line with experimental findings. The mature macrophage population and its activated subfraction revealed a marked proliferation (IFN-alfa group) during treatment. Growth and activation of macrophages may be compatible with their putative function during erythrocytopoietic regeneration and with stimulation of their phagocytic properties.

Effects of the tyrosine kinase inhibitor imatinib mesylate (STI571) on bone marrow features in patients with chronic myelogenous leukemia.

Preliminary data are available about bone marrow (BM) changes in patients with chronic myeloid leukemia (CML) who received the molecularly targeted and highly effective tyrosine kinase inhibitor Imatinib mesylate (STI571). This review is focused on a systematic assessment of BM features detectable at different stages of CML (stable, accelerated, blastic) following long-term (more than 10 months) treatment. By applying enzyme- and immunohistochemistry including monoclonal antibodies visualizing proliferating cell nuclear antigen (PCNA) and apoptosis (anti-apostatin), a more elaborate insight into alterations affecting hematopoiesis and the stroma compartment was gained. In patients with stable-phase CML therapy resulted in a significant reduction in cellularity, neutrophil granulopoiesis and number of megakaryocytes, accompanied by a retrieval of erythroid precursors. In patients with Imatinib as the only treatment morphometric analysis of CD61+ megakaryopoiesis was in keeping with a significant decrease in maturation defects implying a lesser amount of atypical micromegakaryocytes almost consistent with normalization. Moreover, a reduction of the initially enhanced (CD34+) microvessel density was detectable associated with a decrease in luminal distension. Regression of marked to moderate myelofibrosis was recognizable in about 70% of patients especially in the accelerated and blastic phases. The amount of myeloblasts, CD34+ progenitor cells and lysozyme-expressing immature myelomonocytic cells declined with treatment, but recurred in about 19% of patients that developed a leukemic relapse after 21+/-6 months of therapy. Data on proliferative activity and apoptosis in general supported in vitro findings concerning the inhibitory effect of this agent on growth associated with a tendency for stimulated apoptosis, at least in responding patients.

Dynamics of fibrosis in chronic idiopathic (primary) myelofibrosis during therapy: a follow-up study on 309 patients.

Controversial issues in chronic idiopathic myelofibrosis (IMP) are amongst others the evolution of the disease process and the influence of therapy on the dynamics of fibrosis. For this reason, a multicenter observational study was performed on 309 patients with IMF that had a long follow-up including 822 bone marrow biopsies at a median interval of 32 months. In addition to a control group (156 patients) with symptomatic treatment, monotherapy consisted of busulfan (30 patients), hydroxyurea (52 patients), interferon (26 patients) and various combinations (48 patients). Density and quality (reticulin/collagen) of fibers was determined by a semiquantitative scoring system. Independent of therapeutic regimens at the time of the last bone marrow biopsy 67% of the patients with grades 0-2 fibrosis revealed a progression, 42% stable state and 6% regression of myelofibrosis. Because of significant differences concerning frequencies of biopsies and endpoints of examinations, individual changes in the grades of fibrosis were evaluated with regard to treatment applied at standardized intervals of 20 months. According to this calculation no relevant differences in the dynamics of myelofibrosis (progression, stable state) was detectable in the control group compared to the other therapeutic modalities. The few patients with a regression of myelofibrosis usually presented with severe hypoplasia compatible with a myelo-ablative effect by aggressive chemotherapy. In conclusion, persuasive evidence has been produced that myelofibrosis in IMF is characterized by a stepwise progression and that this process is not significantly influenced by current treatment strategies.

Bone marrow features and clinical findings in chronic myeloid leukemia--a comparative, multicenter, immunohistological and morphometric study on 614 patients.

A multicenter, immunohistochemical and morphometric study was performed on diagnostic pretreatment bone marrow biopsies in 614 adult patients with Ph1+ chronic myeloid leukemia (CML) to compare histological features with clinical findings. For identification of megakaryopoiesis we used the monoclonal antibody CD61 and additionally the PAS reaction to determine the subfraction of atypical micromegakaryocytes and precursors. Labelling of erythroid precursors was carried out by a monoclonal antibody directed against glycophorin C. In order to selectively stain macrophages and their activated subset we applied CD68 and the GSA-I lectin. Density of argyrophilic fibers (reticulin plus collagen) was measured following Gomori's silver impregnation method. In accordance with laboratory data morphological variables revealed a comparable amount of congruence in the various groups of CML patients derived from different sources. In about 26% of patients early (reticulin) to advanced (collagen) fibrosis was detectable. Significant correlations were calculated between the extent of myelofibrosis with splenomegaly, anemia and increasing numbers of erythroblasts and myeloblasts in the peripheral blood count. These features were assumed to indicate more advanced stages of the disease process with ensuing transition into myeloid metaplasia and consequently were associated with an unfavorable prognosis. Significant relationships were revealed between the number of CD61+ megakaryocytes and more important, also their precursor fraction with the degree of fibrosis. This result extends previous experimental findings regarding the impact of immature elements of this cell lineage for the generation of myelofibrosis. The significant association of erythroid precursors with the number of mature (resident) macrophages including their activated GSA-I subset may shed some light on their functional involvement in iron turnover and hemoglobin synthesis. A modified histological classification of predominant bone marrow features is introduced. This simplified synthesis staging system (Cologne Classification) is not only associated with certain sets of laboratory data, but also with different survival patterns.

Endoscopic diagnosis of acute intestinal GVHD following allogeneic hematopoietic SCT: a retrospective analysis in 175 patients.

Diagnosis of acute intestinal GVHD (aGVHD) following allogeneic hematopoietic cell transplantation is based on clinical symptoms and histological lesions. This retrospective analysis aimed to validate the 'Freiburg Criteria' for the endoscopic grading of intestinal aGVHD. Grade 1: no clear-cut criteria; grade 2: spotted erythema; grade 3: aphthous lesions; and grade 4: confluent defects, ulcers, denudation of the mucosa. Having excluded patients with infectious diarrhea, we evaluated 175 consecutive patients between January 2001 and June 2009. Setting a cutoff between grade 1 (no change in therapy) and grade 2 (intensification of immunosuppression), macroscopy had a sensitivity of 89.2% (95% confidence interval (CI): 80.4-94.9%), a specificity of 79.4% (95% CI: 69.6-87.1%), a positive-predictive value of 79.6% (95% CI: 70.0-87.2%) and a negative-predictive value of 89.0% (95% CI: 80.2-94.9%). In all, 20% of patients with aGVHD in the lower gastrointestinal tract (GIT) had lesions only in the terminal ileum. In all patients with aGVHD ≥2 of the upper GIT, typical lesions were also found in the lower GIT. Ileo-colonoscopy showed the highest diagnostic yield for aGVHD. In conclusion, the 'Freiburg Criteria' for macroscopic diagnosis of intestinal aGVHD provide high accuracy for identifying aGVHD ≥2.

Remission of refractory Crohn's disease by high-dose cyclophosphamide and autologous peripheral blood stem cell transplantation.

BACKGROUND: Despite advances in immunosuppressive therapy, up to 10% of patients with severe Crohn's disease (CD) remain refractory to conventional treatment. Limited evidence from pilot trials suggests that high-dose immunosuppression and autologous peripheral blood stem cell transplantation (autoPBSCT) may induce remission in these patients, but there is substantial controversy regarding the safety and efficacy of this approach. AIM: To address this issue, a monocentre phase I/II trial of autoPBSCT was performed in patients with refractory CD in our hospital. METHODS: Here, we report on the outcome of 12 patients with refractory CD treated with autoPBSCT. Briefly, CD34(+) -selected PBSCs were harvested after mobilisation therapy with cyclophosphamide and granulocyte-colony stimulating factor. Later, immunoablative conditioning therapy with high-dose cyclophosphamide followed by autoPBSCT was applied and clinical and endoscopic responses were analysed after a mean follow-up of 3.1 years (range 0.5-10.3 years). RESULTS: PBSC harvest following mobilisation chemotherapy was successful in 11/12 patients and resulted in a clinical and endoscopic improvement in 7/12 patients. Subsequent conditioning and autoPBSCT were performed in nine patients and were relatively well tolerated. Among those, five patients achieved a clinical and endoscopic remission within 6 months after autoPBSCT. However, relapses occurred in 7/9 patients during follow-up, but disease activity could be controlled by low-dose corticosteroids and conventional immunosuppressive therapy. CONCLUSION: Immunoablation by cyclophosphamide and autologous peripheral blood stem cell transplantation is safe and effective to induce remission of refractory Crohn's disease, and should be further evaluated in randomised controlled trials.

Polymyositis--an unusual presentation of cGvHD in children.

Polymyositis is a rare manifestation of cGvHD in adult patients following allogeneic BMT. Here, we report on a 2.1-yr-old girl who presented with a facial swelling and rapidly developing respiratory failure eight months after BMT for severe combined immunodeficiency. Possible infectious agents and autoimmune origin other than cGvHD were excluded. The girl responded promptly to steroid therapy and remains well without other signs of cGvHD four months later.