Correspondence 1176 sis. There were several autoantibody positive patients who 2 Tyndall A, Gratwohl A. Immune ablation and stem-cell ther- had never had acute or chronic GVHD. apy in autoimmune disease: Clinical experience. Arthritis Res Furthermore, in a large study on long-term transplanted 2000; 2: 276–280. patients, 36% had a Karnofsky index Ͻ100% but only a 3 Rouquette-Gally AM, Boyeldieu D, Prost AC, Gluckman E. few of them had active cGVHD.7 This fits with earlier Autoimmunity after allogeneic bone marrow transplantation. reports that the occurrence of autoantibodies after HSCT A study of 53 long-term-surviving patients. Transplantation 1988; 46: 238–240. does not correlate with cGVHD but might be rather the 4 Chan EY, Lawton JW, Lie AK, Lau CS. Autoantibody forma- expression of an abnormal B cell and/or T cell reconsti- 3–5,8–10 tion after allogeneic bone marrow transplantation: correlation tution. with the reconstitution of CD5ϩ B cells and occurrence of Therefore, we hypothesize that long-term survivors after graft-versus-host disease. Pathology 1997; 29: 184–188. allogeneic HSCT are at risk for a skewed immune reconsti- 5 Hebart H, Einsele H, Klein R et al. CMV infection after allo- tution with altered immune response leading to late second- geneic bone marrow transplantation is associated with the ary ‘auto’-immune like phenomena. More detailed and occurrence of various autoantibodies and monoclonal gammo- longer analyses are needed to confirm our observation. pathies. Br J Haematol 1996; 95: 138–144. 6 Quaranta S, Shulman H, Ahmed A et al. Autoantibodies in M Trendelenburg1 1Division of Medicine, Medical human chronic graft-versus-host disease after hematopoietic M Gregor2 Clinic B, University Hospital cell transplantation. Clin Immunol 1999; 91: 106–116. J Passweg2 Basel, Basel, Switzerland; 7 Socie´ G, Stone JV, Wingard JR et al. Long-term survival and A Tichelli2 2Division of Hematology, late deaths after allogeneic bone marrow transplantation. New A Tyndall3 University Hospital Basel, Engl J Med 1999; 341:14–21. A Gratwohl2 Petersgraben 4, 4031 Basel, 8 Vavassori M, Maccario A, Comoli P et al. Restricted TCR Switzerland; 3Division of repertoire and long-term persistence of donor-derived antigen- ϩ Rheumatology, University Hospital experienced CD4 T cells in allogeneic bone marrow trans- Basel, Basel, Switzerland plantation recipents. J Immunol 1996; 157: 5739–5747. 9 Roux E, Helg C, Chapuis B et al. T-cell repertoire complexity after allogeneic bone marrow transplantation. Hum Immunol References 1996; 48: 135–138. 10 Leroy E, Calvo CF, Divine MF et al. Persistence of 1 Lawley TJ, Peck GL, Moutsopoulos HM et al. Scleroderma, T8ϩ/HNK-1ϩ suppressor lymphocytes in the blood of long- Sjo¨gren-like syndrome, and chronic graft-versus-host disease. term surviving patients after allogeneic bone marrow trans- Ann Intern Med 1977; 87: 707–709. plantation. J Immunol 1986; 137: 2180–2189.

A patient with anaphylactoid hypersensitivity ine, 158 mg (2.5 mg/kg per standard protocol for graft-ver- to intravenous cyclosporine and sus-host disease prophylaxis (GVHD)) in 50 ml of 5% dex- trose in water was started, to be given over 4 h. After subcutaneous phytonadione (vitamin K1) infusion of 2 ml, the patient complained of flushing, nausea and urinary/fecal incontinence. On examination, vital signs were heart rate 100, blood pressure 240/120 and respiratory Intravenous (i.v.) phytonadione (vitamin K ), i.v. cyclospo- 1 rate 22. Diphenhydramine, 50 mg i.v. was administered and rine and paclitaxel have all been associated with anaphyl- the symptoms completely resolved. Cyclosporine was dis- axis most likely caused by their vehicle, polyethyloxylated castor oil.1–3 Polyethyloxylated castor oil (PEO-CO) is a continued and i.v. tacrolimus was begun for GVHD pharmaceutical vehicle marketed as Cremophor EL by prophylaxis. However, tacrolimus had to be stopped after BASF (Ludwigshafen, Germany). There are little experi- 3 weeks due renal toxicity. At that time she was cautiously mental data, but the reactions have been classified as ana- restarted on oral cyclosporine (non PEO-containing), which phylactoid.4 We report the first case of a patient with ana- she tolerated well. phylactoid reactions to two drugs containing PEO-CO and On hospital day 16, the patient developed gastrointestinal the first case of an anaphylactoid reaction to subcutane- bleeding. International normalized ratio (INR) was 9.6. ous phytonadione. Phytonadione (AquaMEPHYTON Merck, West Point, PA, A 40-year-old female with a diagnosis of acute myelog- USA), 10 mg was administered subcutaneously. Immedi- enous leukemia (AML-M4) was admitted to hospital for ately after injection, the patient complained of dyspnea. On matched related allogeneic peripheral blood stem cell trans- physical examination, vital signs were heart rate 155, blood plantation. Allergic history was significant for urticaria fol- pressure 160/135, and respiratory rate 33. Flushing and lowing oral erythromycin. There was no personal history wheezing were present. The patient was treated with nebul- of asthma, anaphylaxis or allergic rhinitis. She had never ized albuterol and ipratropium, 100 mg i.v. methylpredniso- previously been treated with phytonadione, cyclosporine or lone and 50 mg i.v. diphenhydramine. The patient’s symp- other medications containing PEO-CO. toms resolved over several minutes. The patient later One day prior to the stem cell transplant, i.v. cyclospor- tolerated oral phytonadione (non-PEO-containing) well.

Bone Marrow Transplantation Correspondence 1177 The patient did not undergo skin testing because of References cutaneous acute graft-versus-host disease, which was present at the time. 1 Rich EC, Drage CW. Severe complications of intravenous phy- Attempts to demonstrate an IgE antibody in the patient’s tonadione therapy. Two cases with one fatality. Postgrad Med serum to PEO-CO using solid phase radio allergosorbent 1982; 72: 303–306. and dot blot nitrocellulose methods were negative. 2 Ciesielski-Carlucci C, Leong P, Jacobs C. Case report of ana- We conclude this patient most likely had anaphylactoid phylaxis from cisplatin/paclitaxel and review of their hypersen- sitivity reaction profiles. Am J Clin Oncol 1997; 20: 373–375. (non-IgE mediated) hypersensitivity reactions to the PEO- 3 Volcheck GW, Van Dellen RG. Anaphylaxis to intravenous CO contained in the phytonadione and cyclosporine admin- cyclosporin and tolerance to oral cyclosporin: case report and istered. We recommend extreme caution and possibly review of the literature. Ann Allergy Asthma Immunol 1998; avoidance when considering administration of a medication 80: 159–163. containing PEO-CO to a patient with a history of reaction 4 Anonymous. Executive summary of disease management of to another medication containing PEO-CO. drug hypersensitivity: a practice parameter. Ann Allergy Asthma Immunol 1999; 83: 665–700. DL Riegert-Johnson 1Department of Internal Medicine, S Kumar Mayo Clinic, 200 First Street SW, GW Volcheck Rochester, MN 55905, USA; 2Department of Hematology and Oncology, Mayo Clinic, Rochester, MN, USA; and 3Division of Allergic Diseases, Mayo Clinic, Rochester, MN, USA

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