Summary:Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Patients with severe aGVHD not responding to treatment with steroids have a poor prognosis. We treated four patients with severe aGVHD refractory to steroids with infliximab, a chimeric human/mouse antiTNF␣ antibody. Patients (CML 2, MM 1, AML 1) developed grade III-IV GVHD at a median of 34 days (range 15-76) after myeloablative PBSCT (two), donor lymphocyte infusion for relapsed CML (one) or non-myeloablative PBSCT (one), respectively. All patients had severe intestinal involvement in addition to skin and/or liver disease and had received treatment with high-dose steroids (four) for a median of 11 days (range 5-17) in addition to CsA (four) and MMF (three). Infliximab (10 mg/kg) was given once a week until clinical improvement. In three of four patients a complete resolution of diarrhea and significant improvement of skin and liver disease were observed. Two patients received one, one patient two and one patient three infliximab infusions. At present two patients are alive Ͼ200 days after therapy, one with limited cGVHD. Two patients died, one of progressive malignant disease without GVHD and one of refractory GVHD. Infliximab is apparently an active drug for the treatment of aGVHD. Bone Marrow Transplantation (2001) 28, 47-49. Keywords: graft-versus-host disease; TNF-␣; infliximab Acute GVHD causes significant morbidity and mortality after allogeneic haematopoietic cell transplantation despite the use of effective prophylactic regimens. remissions in the majority of patients. Individuals who fail steroid therapy have been treated with a variety of agents including MMF, ATG, OKT3 and antibodies to the interleukin-2 receptor alone or in combination. 2,3 Response rates have varied between 15 and 60%, but, in part due to infectious complications and relapse of the underlying disease, survival has been low. Early studies have suggested a beneficial effect of treatment strategies that block the activity of TNF␣, which is the key cytokine in the inflammatory cascade of aGVHD. 4 We treated four patients with severe steroid refractory GVHD with the chimeric anti-TNF␣ antibody infliximab (Remicade; Centocor, Leiden, The Netherlands), which is approved for the clinical use in rheumatoid arthritis and Crohn's disease. Case 1A 40-year-old male patient with CML in first chronic phase was given an allogeneic peripheral blood stem cell (PBSC) transplant (4.07 × 10 6 CD34 + cells per kg) from his HLAidentical sister after conditioning with busulfan (16 mg/kg) and cytoxan (120 mg/kg). He received CsA and MMF for GVHD prophylaxis. The post-transplant clinical course was uneventful until at day 15, when the patient developed acute GVHD III-IV with cutaneous, hepatic and severe intestinal involvement. Steroid treatment was initiated, but the diarrhea continued. After 5 days with steroids Ͼ10 mg/kg/day without improvement he received a single dose of infliximab (10 mg/kg). Stool frequency star...
We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×10/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13). Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1-135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia,
A MRI of the lumbal spine was performed on a patient with lumbago. Besides the fact of no evidence for a myelopathy caused by a herniated disc a both-sided iliac vein thrombosis could be seen. In further examination the coincidence of a congenital absence of vena cava inferior with distinctive collateral vessel systems over lumbal and spinal veins and heterozygosis for Factor V Leiden abnormality could be identified as cause for thrombosis. It is very likely that symptoms developed as a result of spinal vein hyperplasia and consecutive myelon compression.
2057 Purpose of the study: Chemotherapy (CT) induced neutropenia (CIN) is a common complication in the treatment of cancer and often leads to modifications of antineoplastic treatment. Granulocyte-colony stimulating factors (G-CSF) are frequently used to prevent or treat CIN in cancer patients. The non-interventional observational study HEXAFIL on the use of biosimilar filgrastim (EP-2006) was conducted to provide further insight into its therapeutic efficacy and routine clinical use in Germany, especially in compliance with guidelines on the use of G-CSF (EORTC, ASCO). Methods: 1460 patients who signed informed consents are to be enrolled at 100 German sites. Data is documented for up to 3 consecutive filgrastim-supported CT-cycles. Rates of modified CT-treatments (dose modification/discontinuation of drug) are calculated by the number and percentage of patients affected; data presented are based on the first CT-cycle. Inclusion/Exclusion criteria: www.germanctr.de. Results: By 7/2012, data of 955 patients were available. Patients' mean age was 59 years (19 to 89), 75% of them being female. Most common tumour entities were breast cancer (57.2%), NHL (10.7%), lung cancer (7.6%), ovarian cancer (4.0%) and Hodgkin lymphoma (3.1%). Substances most commonly used for chemotherapy were cyclophosphamide (50.7%), epirubicin (33.2%), docetaxel (23.6%), 5-fluorouracil (20.9%) and doxorubicin (15.6%). In line with published data only 1.9% of all patients experienced febrile neutropenia (FN), 8.7% neutropenic complications and 14% had leukopenia CTC 4 at nadir. As expected and according to guidelines the majority of patients received primary (39.3%, PP) or secondary prophylaxis (32.9%, SP) with biosimilar filgrastim, however, 25.8% were treated on demand (TX, i.e. after having experienced neutropenic complications in the first documented CT cycle or a drop in leukocytes putting the patient at acute risk of neutropenic complications). Interestingly, if viewed by the presence of baseline leukopenia, 76.9% of all patients without leukopenia (CTC 0) received G-CSF prophylaxis (PP/SP) but only 46.1% of all patients with leukopenia CTC 3/4. In patients without baseline leukopenia receiving filgrastim for PP, leukopenia CTC 3/4 at nadir was present in 32.9%, whereas in SP it was 50.6% and in TX 70.8%. Median filgrastim treatment duration was 4 d (1 to 14). Patients with PP received median 5 days of treatment starting on median day 6 after CT, whereas SP and TX patients were treated on median day 8 and 9, respectively, for a median duration of 3 days each. Accordingly, patients with neutropenic complications received treatment starting on median day 8 for 3 days (median), whereas patients without neutropenic complications started on median day 7 for 5 days (median); moreover, patients with FN only started biosimilar filgrastim therapy on median day 9. 93.9% of all documented patients received CT without any modification; in 4.6% of patients the dose of chemotherapy was modified and in 1.4% a chemotherapy drug was discontinued. Data indicate that patients with earlier and longer filgrastim treatment showed less chemotherapy disturbances, FN and neutropenic complications. Conclusions: Approximately 94% of all documented patients received filgrastim-supported CT-cycles without any modification of the CT-regimen. Yet, there is still room for improvement in prevention of CIN/FN in cancer patients as reflected by median start/treatment days and number of neutropenic complications. Moreover, daily injections should not impact the prophylactic use of G-CSF as revealed by self-assessment questionnaires in which patients reported handling of the needle guard system and of the pre-filled syringes to be easy or very easy (97.7% and 97.8%, respectively and calculated on questionnaires evaluable). Disclosures: Tesch: Amgen, Astra Zeneca, Boehring Ingelheim, Celgene, GSK, Hexal, Janssen Cilag, Lilly, Merck, Novartis, Pfizer, Roche: Honoraria; Amgen, Astra Zeneca, Boehring Ingelheim, Celgene, GSK, Hexal, Janssen Cilag, Lilly, Merck, Novartis, Pfizer, Roche; Sanofi Aventis: Consultancy. Abenhardt:Hexal: Honoraria. Dietze:Hexal: Honoraria. Chang:Hexal: Employment. Ottillinger:Hexal, Sandoz: Consultancy, Honoraria.
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