Case Report Resolution of Chronic Idiopathic Thrombocytopenia Purpura Following Syngeneic Peripheral Blood Progenitor Transplant

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Case Report Resolution of Chronic Idiopathic Thrombocytopenia Purpura Following Syngeneic Peripheral Blood Progenitor Transplant Bone Marrow Transplantation (2002) 29, 87–89 2002 Nature Publishing Group All rights reserved 0268–3369/02 $25.00 www.nature.com/bmt Case report Resolution of chronic idiopathic thrombocytopenia purpura following syngeneic peripheral blood progenitor transplant MA Zaydan1, C Turner2 and AM Miller1 1Tulane Cancer Center, Tulane Bone Marrow Transplant Program and Department of Medicine, Tulane University3, New Orleans, LA, USA; and 2Children’s Clinic, Lake Charles, LA, USA Summary: Case report Idiopathic thrombocytopenia purpura (ITP) is an Past history acquired disease of children and adults characterized The patient, a 19-year-old male, was referred to the Tulane by a low platelet count, an essentially normal bone mar- Bone Marrow Transplant program in January 2000 after a row, and absence of evidence for other disease. We long history of chronic refractory ITP. He was diagnosed report the use of syngeneic peripheral blood progenitor with ITP at the age of 5 in 1986. He was treated with ster- transplantation (PBPT) in a 19-year-old male with oids and had modest unsustained responses. Similarly, he chronic refractory ITP since the age of 5. Engraftment had transient responses to intravenous immunoglobulin was successful and has resulted in resolution of his dis- infusions (IVIG). The patient underwent a therapeutic ease. We conclude that syngeneic PBPT is a potentially splenectomy in February 1987, his ITP resolved and his curative option for refractory ITP. platelet count normalized for a period of approximately 3 Bone Marrow Transplantation (2002) 29, 87–89. DOI: years. Recurrent ITP was precipitated by an infectious epi- 10.1038/sj/bmt/1703336 sode associated with fever, leukocytosis and thrombocyto- Keywords: idiopathic thrombocytopenia purpura; hema- penia. Subsequently, the patient developed chronic ITP topoietic progenitor cell transplantation; autoimmune dis- with occasional spontaneous bruising but no bleeding epi- ease; chronic ITP; refractory ITP sodes and a platelet count range of 10 to 50 000 (Figure 1a). This continued until approximately 3 years prior to a Idiopathic thrombocytopenia purpura (ITP) is an acquired 300 disease of children and adults characterized by a low plate- 250 let count, an essentially normal bone marrow, and absence 200 of evidence for other disease. The clinical syndromes of 150 ITP are distinct between children and adults: Childhood 100 ITP characteristically is acute in onset and resolves spon- 50 taneously in most cases within 6 months,1 whereas adult 0 ITP typically has an insidious onset and rarely resolves Platelets (thousands) spontaneously.2–5 The incidence of ITP in children is esti- 05/21/1990 05/21/1991 05/21/1992 05/21/1993 05/21/1994 05/21/1995 05/21/1996 05/21/1997 05/21/1987 05/21/1988 05/21/1989 mated to be approximately 46 new cases per million per 05/21/1986 year. Patients who fail to maintain a normal platelet count Date after conventional therapies are labeled as chronic refrac- b 400 tory ITP patients. Treatment modalities include glucocor- 350 ticoids, splenectomy, intravenous immunoglobulin (IVIG), 300 250 anti-Rh (D) immune globulin, azathioprine, cyclophos- 200 phamide, vinca alkaloids, danazol, vitamin C, combination 150 chemotherapy, cyclosporine, dapsone and interferon- 100 50 1–5 ␣-2b. Recent information suggests that the anti-CD20 0 antibody, rituximab may be beneficial.6 To date, limited information exists on the use of hematopoietic progenitor Platelets (thousands) cell transplantation as a treatment for this disease.7–10 01/01/2001 11/01/2000 03/01/2001 05/01/2001 07/01/2001 09/01/2001 01/01/2000 03/01/2000 07/01/2000 09/01/2000 11/01/1999 05/01/2000 01/01/1999 03/01/1999 09/01/1999 05/01/1999 07/01/1999 Date Correspondence: Dr AM Miller, Tulane University School of Medicine, 1430 Tulane Avenue, TW 5, New Orleans, LA 70112-2699, USA Figure 1 (a) Sequential platelet counts 1986–1998; (b) sequential plate- Received 11 October 2001; accepted 21 October 2001 let counts 1998–2001. Resolution of ITP after syngeneic PBPT MA Zaydan et al 88 presentation to our center. During the 3 years preceding In February 2000, patient was started on rituximab (anti- this referral platelet counts were frequently less than CD20 antibody). He received a total of 8 weekly treatments 10 000. During the past 10 years, the patient had multiple at a dose of 375 mg/m2/week with no response. The pres- episodes of febrile illnesses of various etiologies that pre- ence of an accessory spleen was excluded by abdominal cipitated more severe thrombocytopenia and required CT and tagged red blood cell scans. repeated hospitalization and attempts at different treatment modalities for his ITP. His treatment prior to presentation Stem cell transplant to our center included IVIG, rhoGAM, steroids, cyclophos- phamide and cyclosporine. Various dosages and combi- The patient had a healthy male twin confirmed by molecu- nations of the above listed medications were used with lar studies to be identical. In view of the debilitating nature unsustained responses (Table 1). He received corticostero- of his disease and the low risk of GVHD, we proceeded to ids in at least low doses for the majority of the preceding a syngeneic BMT in October 2000 when the patient was 10 years. 20 years old. Pre-transplant investigations including cardiac For the previous 2 years his thrombocytopenia had ejection fraction, pulmonary function tests, renal and liver become very severe with a platelet count below 10 000 function were all normal. Conditioning consisted of a single necessitating aggressive immunosuppressive treatments fraction of total body irradiation (TBI) given at a dose of (Figure 1b). This affected his functional status and resulted 5.5 Gy and cyclophosphamide at a dose of 50 mg/kg/day in several side-effects including infections, febrile illnesses, intravenous infusion over 1 h for 3 days. He also received severe obesity and other long-term effects of prolonged Mesna prophylactically for hemorrhagic cystitis during the term steroids. administration of cyclophosphamide. He then received a G- Table 1 ITP treatments: dates, duration, maximal response and duration Agent Doses Dates used Maximal Maximal response duration of by platelet response count ϫ1000 Prednisone High dose (40–80 mg q d) September 86 96 1 week October 86 September 98 November 98 February 99 April 99 May 99 June 99 October 99–January 00 April 00–June 00 August–September 00 Prednisone Low dose Ͻ40 mg q d September 86 37 2 weeks January 99–February 99 August 99 September 99–October 99 March 00–April 00 August 00 IVIG 2 g/kg over 5 days December 86 155 1 week 1 g/kg q week September 98 October 98 February 99 Dexamethazone 40 mg q d ϫ 4 days December 98 150 2 week February 99 April 99 May 99 July 00 September 00 Vincristine ? Dose October 98 No response N/A Rhogam ? Dose August 98 No response N/A Cyclophosphamide 1 g/m2 February 99–July 99 No response N/A Cyclosporine 100–400 mg q d August 99–December 99 No response N/A Splenectomy February 87 274 3 years IV Solumedrol 50 mg i.v. q 6 h August 98 97 1 week January 00 Rituxan, total of 8 cycles 375 mg/m2 q week April 00–June 00 No response None Bone marrow 10/11/00 374 Sustained transplantation Bone Marrow Transplantation Resolution of ITP after syngeneic PBPT MA Zaydan et al 89 CSF-stimulated syngeneic peripheral blood progenitor cell an identical twin donor, a factor that markedly lowers the transplant. The mononuclear cell dose was 10.3 ϫ 108/kg chance of GVHD. In addition, we also considered the mor- containing a CD34 dose of 12.7 ϫ 106/kg. bidity and poor quality of life of this young man because In the post-transplant period, the patient developed mye- of his disease. The post-transplant course was relatively losuppression, neutropenia, anorexia and gastrointestinal unremarkable, minimal complications occurred and there toxicity requiring total parenteral nutrition support. Recov- was prompt recovery of granulocytes and red cells. No ery was complicated by a Staphylococcus line infection that GVHD prophylaxis was given and no GVHD documented. responded to antibiotics. The patient successfully engrafted Platelet recovery was somewhat delayed (55 days post with a neutrophil count Ͼ0.5 ϫ 109 by day 8. He was transplant) but his platelet count normalized and remains discharged home on day 12 post transplant. In the in the normal range. In this case syngeneic PBPT appears to post-transplant period, he required no red blood cell trans- be a safe and effective treatment for chronic ITP. Syngeneic fusions, however, he received a total of four platelet trans- transplant for ITP should be considered when other fusions. His platelet count was 12 000 upon discharge. He modalities have failed after careful analysis of the risks and had a low platelet count for 1 month that gradually benefits of transplantation are compared to the risks of increased to 98 000 on day 50 and reached a normal level continued ITP and other therapies. of 148 000 on day 55. His platelet counts at 6 and 11 months (most recent) post transplant were 374 000 and 373 000, respectively. The patient is off all therapy and he References is starting to regain a normal life. 1 Blanchette V, Carcao M. Approach to the investigation and management of immune thrombocytopenic purpura in chil- Discussion dren. Semin Hematol 2000; 37: 299–314. 2 Bussel JB. Overview of idiopathic thrombocytopenia purpura: To our knowledge, this is the first case report of syngeneic new approach to refractory patients. Semin Oncol 2000; 27: PBPT for ITP. The transplant procedure was largely 91–98.
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