Successful treatment of thrombocytopenia and hemolytic anemia with IvIG in a patient with lupus-like syndrome after mismatched related PBSCT

Abstract

Summary:Hematopoietic stem cell transplantation (HSCT) is a treatment option for autoimmune diseases but can also cause clinical features similar to those of autoimmune diseases. In some of these cases the autoimmune-like condition is associated with autoimmune cytopenia, a complication that can be unresponsive to established treatment strategies and which may be fatal. The majority of cases reported on immune hemolytic anemia have been of alloimmune origin due to ABO red blood cell antigen incompatibilities between donor and recipient. We now report a patient with a lupus-like syndrome, presenting with severe thrombocytopenia and hemolytic anemia 9 months after HLA-mismatch, ABO compatible-related PBSCT who experienced no response to high-dose steroids, but who had a sustained response to repeated IvIG therapy. Bone Marrow Transplantation (2001) 27, 337-340. Keywords: autoimmune cytopenia; hematopoietic stem cell transplantation; lupus-like syndrome; alloimmunity; IvIG Hematopoietic stem cell transplantation (HSCT) can cause clinical symptoms characteristic of autoimmune diseases like myasthenia gravis, immune thyroiditis, as well as immune cytopenia. 1-11 Especially, autoimmune cytopenia is mostly refractory to standard therapeutic approaches. 2,3 We herein report a patient with a lupus-like syndrome associated with hemolytic anemia and severe thrombocytopenia after HSCT. Patient characteristicsNine months (day +277) after a mismatched related allogeneic stem cell transplant (PBSCT) for CML in first CP, a 38-year-old patient presented with weight gain, general GvHD prophylaxis consisted of cyclosporine (CYA) starting on day −3, prednisolone starting on day +7 after transplantation and MTX given as a short course on days +1, +3 and +6 at a dose of 15 mg/m 2 and twice at 10 mg/m 2 , respectively. Engraftment (leukocyte count Ͼ1000 × 10 9 /l, neutrophil count Ͼ0.5 × 10 9 /l) occurred on day +21 after PBSCT. He developed slight cutaneous GVHD grade I-II which responded promptly to increased immunosuppression with prednisolone (0.7 mg/kg bw × day) for 1 week, then tapered, and mycophenolate-mofetil (MMF) (2 g/day) for 3 months.CMV reactivation, as diagnosed by CMV-PCR, occurred 2 months after PBSCT (recipient CMV IgG positive, donor CMV IgG negative). This was successfully treated with ganciclovir, but the PCR became positive again shortly after cessation of therapy. He therefore received cidofovir as maintenance for 2 months.Immunosuppressive therapy on admission consisted of prednisolone 5 mg/day and CYA 150 mg/day given orally (blood level 284 ng/ml). Clinical findingsAs papular cutaneous lesions were the main clinical finding a viral infection was suspected, possibly herpes virus or VZV reactivation. CMV testing had been negative for the last 4 months. However, the CMV-PCR was positive at the time of admission. He was treated with foscarnet to avoid further myelosuppression in a graft which was already suboptimal. Testing for VZV and HSV was negative.Within a few days of admission the patient developed

Autoimmune Complications after Hematopoietic Stem Cell Transplantation in Children with Nonmalignant Disorders

“…One case of ITP received a major ABO-mismatched graft for aplastic anemia, and two cases of ITP received a sex-mismatched graft. ITP has been reported early after allogeneic HSCT [8]. It is not clear whether cytopenia is related to the process of HSCT or to autoimmune dysregulation.…”

Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used

“…[15][16][17] The spectrum of autoimmune disorders includes autoimmune cytopenias most frequently, but has also included autoimmune thyroiditis, 18 myasthenia gravis, 19 rheumatoid arthritis, 20 and a lupuslike illness. 2 Acquired hemophilia due to factor VII antibodies after HSCT has been described in 8 patients, 21 but acquired hemophilia due to factor VIII inhibitors has been reported only once to our knowledge, having occurred in a patient with MS after auto-HSCT during which he received conditioning with ATG. 22 The authors of the latter report concluded the coexistence of 3 factors (underlying autoimmunity, auto-HSCT, and use of interferon-beta) predisposed the patient to developing this autoimmune complication.…”

“…[1][2][3][4] The underlying mechanism for the development of autoimmunity is postulated to involve impaired function of regulatory T cells allowing selfreactive T cells to act unchecked. 5 Delayed T-cell reconstitution following transplantation may thus predispose patients to the development of a secondary autoimmune disorder.…”

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report

“…Intravenous immunoglobulin may be effective in certain cytopenias that have not improved after steroid treatment [78,80] (Table 9). Growth factor use has not been formally evaluated in chronic GVHD patients with persistent cytopenias.…”