Acute Graft-Versus-Host Disease in Recipients of Bone-Marrow Transplants From Identical Twin Donors

Rappeport, Joel M.; Reinherz, Ellis L.; Mihm, Martín C.; Lopansri, Sumala; Parkman, Robertson

doi:10.1016/s0140-6736(79)90644-5

Cited by 121 publications

(46 citation statements)

References 27 publications

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“…Findings often persist for 1-3 weeks followed by a rapid dissipation of signs and symptoms. Skin involvement is most common, 9,10 while gastrointestinal or hepatic involvement is though to be much less frequent, 11,12,27 but may be underreported. For example, in a recent single-center retrospective analysis, Holmberg et al 11 suggested a 13% incidence of intestinal auto-GVHD.…”

Section: Incidence and Clinical Characteristicsmentioning

confidence: 99%

“…In the late 1970s Rappeport et al 27 reported the occurrence of GVHD in humans following syngeneic bone marrow transplantation, which prompted an exploration into the biologic mechanisms underlying this phenomenon, as major or minor histocompatibility antigen mismatches between donor and recipient were at that time thought to be absolutely required for the initiation of GVHD. Interestingly, Glazier et al 13 developed a preclinical transplant model of auto-GVHD.…”

Section: Animal Models Of Auto-gvhdmentioning

confidence: 99%

See 1 more Smart Citation

Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance

Kline

Subbiah

Lazarus

et al. 2007

Bone Marrow Transplant

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Section: Incidence and Clinical Characteristicsmentioning

confidence: 99%

Section: Animal Models Of Auto-gvhdmentioning

confidence: 99%

Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance

Kline

Subbiah

Lazarus

et al. 2007

Bone Marrow Transplant

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“…There have been only a few cases of autoimmune thrombocytopenia reported after BMT, all of which were in adults. 12,[17][18][19] There are no reports of similar cases in children. Both patients also had large intracerebral hemorrhages not described in the adult cases.…”

Section: Discussionmentioning

confidence: 99%

Acquired autoimmune thrombocytopenia post-bone marrow transplantation for severe combined immunodeficiency

Ting

Ziegler

Vowels

1998

Bone Marrow Transplant

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Summary:Children with severe combined immunodeficiency (SCID) have profoundly diminished humoral and cellular immunity resulting in death during infancy unless immune reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post-bone marrow transplantation can be seen in relation to infection, graft-versus-host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune dysregulation. We report two cases of severe AITP following BMT for SCID. Both cases developed large intracerebral hemorrhages from which one died. Autoimmune thrombocytopenia in this setting can be life-threatening and we recommend early and active intervention. Keywords: autoimmune thrombocytopenia; BMT; severe combined immunodeficiency Severe combined immunodeficiency (SCID) is a syndrome describing children with profound cellular and humoral immune dysfunction attributable to different causes such as enzyme deficiencies (ADA, PNP), 1,2 T cell defects, defective HLA expression, as well as the more common ␥c deficiency. 3 For these patients, with the exception of ADA deficiency, bone marrow transplantation (BMT) is the therapy of choice. 4,5 The time taken for engraftment of the marrow cells and immune reconstitution varies depending on multiple factors. These include: (a) the use of T cell depleted 6-8 vs unfractionated bone marrow cells; 9,10 (b) pre-transplant conditioning; (c) the presence or absence of graft-versushost disease (GVHD) and its treatment; 11 (d) concomitant infections; and (e) the general status of the patient. 12 During this early post-transplant period, the immune imbalance observed as the donor immune system emerges, modified by the host, results in well described symptom complexes such as GVHD. 11,[13][14][15][16] This underlying immune dysregulation may also result in autoimmune cytopenias. 12,17 We report two cases of severe AITP following a haploidentical, T cell-depleted allogeneic BMT for SCID. Case report Patient AA girl presented with recurrent respiratory infections and persistent diarrhea and was diagnosed with T − B + SCID with normal adenosine deaminase (ADA) and purine nucleophosphorylase (PNP) levels at 3 months of age. Her hematological and immunological profile at presentation were: hemoglobulin (Hb) 11.8 g/dl, white cell count (WCC) 4.6 × 10 9 /l, platelet count (plat) 225 × 10 9 /l, Ig G/A/M of 1.7, Ͻ 0.1, 0.3 g/l, respectively, CD3 Ͻ0.02 (normal 0.9-1.6), CD4 Ͻ0.02 (normal 0.7-1.2), CD8 Ͻ0.02 (0.3-9.7), CD19 1.74 (0.16-0.36) and NK cells 0.39 (0.13-0.35) × 10 9 /l. Response to mitogen was not performed due to the almost absent number of T cells. She underwent a T cell-depleted (soybean lectin sheep E-rosetting), haploidentical BMT without conditioning from her father at 4 months of age. Engraftment was documented on day +21 post-transplant by fluorescent in situ hybridization (FISH) studies for XY cells and the post-transplantation course was complicated by respiratory failure, acute renal failure and graft-versus-host disease (GVHD) involving skin and gastrointestinal tract...

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“…Acute skin GVHD is described in the context of autologous and syngeneic BMT. 3,[5][6][7][8][9][10] The mechanism is thought to be release of autoreactive T cells directed at HLA class II antigens 2,11,12 by failure of apoptotic deletion due to thymic damage by TBI. 13,14 This mechanism may be enhanced by CYA which breaks selftolerance 15 and has been used to induce autologous GVHD.…”

Section: Discussionmentioning

confidence: 99%

Acute skin GVHD following syngeneic BMT for CLL

Deane

Singer

Lawler

et al. 1998

Bone Marrow Transplant

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Summary:A 41-year-old woman received a syngeneic BMT for CLL and subsequently developed acute skin GVHD. Transfusion-related allogeneic GVHD was excluded on the basis of an unchanged HLA type in circulating lymphocytes. Short tandem repeat PCR was used to confirm syngeneicity between donor and recipient. The patient had a personal and family history of autoimmune disease which may have made her particularly susceptible to development of syngeneic GVHD. The distinction between allogeneic and syngeneic or autologous GVHD is important because of therapeutic implications. Keywords: GVHD; syngeneic BMT; CLL; chimerism We report the case of a 41-year-old woman who received a syngeneic BMT for CLL and subsequently developed histologically proven acute grade 2 skin GVHD requiring treatment, including high-dose corticosteroids. The HLA type of circulating lymphocytes remained unchanged. Short tandem repeat (STR)-PCR analysis of pre-BMT DNA extracted from donor and recipient indicated identity between donor and recipient supporting the diagnosis of syngeneic GVHD. Syngeneic and autologous GVHD has been described in animal models. 1,2 Mild and self-limiting acute skin GVHD is thought to occur in 8% of patients receiving autologous and syngeneic BMT. 3 Case reportThe patient presented with stage B CLL and Sjogren's syndrome in 1992. There was a strong family history of autoimmune disease. The patient, her mother and identical twin sister all had hypothyroidism and the patient's mother also had SLE. The patient required intermittent treatment for CLL but, by 1994, her disease had advanced to cause bone marrow failure. She showed a good response to six courses of fludarabine with a reduction in bone marrow lymphocytic infiltration to 40%. She subsequently received a syngeneic BMT following CY 120 mg/kg and single fraction TBI (750 cGy at 16 cGy/min) conditioning. Both recipent and donor were CMV seronegative. At the time of transplant, the patient had no evidence of active autoimmune disease. She received irradiated blood products throughout. The transplant was uncomplicated with haemopoietic recovery (Ͼ0.5 × 10 9 /l neutrophils, Ͼ20 × 10 9 /l platelets) at day 25. Over the next week she developed a generalised skin rash which progressed to desquamation. She was systemically well with no evidence of infection. She had not been commenced on any new drugs in the preceding 3 weeks. A skin biopsy showed the appearances of grade II GVHD with basal cell degeneration and a focal lymphocytic infiltration of the epidermis (Figure 1). Although the patient had been designated to receive irradiated blood products, and showed no deterioration in bone marrow function, we felt that transfusion acquired GVHD should be excluded because of therapeutic implications. The HLA type of the circulating lymphocytes was determined and was unchanged. Pre-BMT DNA extracted from the recipient and donor was compared using a panel of STR markers as previously described. 4 Seven markers were tested (see

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Acute Graft-Versus-Host Disease in Recipients of Bone-Marrow Transplants From Identical Twin Donors

Cited by 121 publications

References 27 publications

Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance

Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance

Acquired autoimmune thrombocytopenia post-bone marrow transplantation for severe combined immunodeficiency

Acute skin GVHD following syngeneic BMT for CLL

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