High Frequency of Graft-Versus-Host-Like Syndromes Following Syngeneic Bone Marrow Transplantation

Summary:In a multicentre retrospective EBMT database study, we analysed factors influencing outcome in 38 patients with MDS/sAML who were transplanted with stem cells from their syngeneic twin and compared those to 1444 patients who were transplanted from an HLA-identical sibling. The median time to leukocyte and platelet engraftment was faster in the twin group: 14 vs 17 (P ¼ 0.02) and 16 vs 26 days (P ¼ 0.09), respectively. The 5 years cumulative incidence of treatment-related mortality (TRM) was higher in the sibling than in the twin group (38 vs 27%; P ¼ 0.05). The 5 year cumulative incidence of relapse was 32% (95% CI: 29-35%) for the siblings and 39% (95% CI: 26-60%; P ¼ 0.6) for the twins. A trend for better 5-years disease-free and overall survival was observed in the twin group: 34% (95% CI: 14-54%) vs 28% (95% CI: 25-31%; P ¼ 0.2) and 36% (95% CI: 15-57%) vs 32% (95% CI: 29-35%; P ¼ 0.09), respectively. In a multivariate analysis, stem cell transplantation from identical twins had a lower TRM: HR: 0.4 (95% CI: 0.2-0.9; P ¼ 0.03). The relapse rate was similar for both groups with a HR of 1.2 (95% CI: 0.07-2.1; P ¼ 0.5), with a better survival for the twins: HR 0.6 (95% CI: 0.4-1.0; P ¼ 0.07). We conclude that twin transplantation in MDS/sAML is associated with a similar relapse risk, a lower TRM and a trend for better overall survival in comparison to transplantation from HLA-identical siblings.

Section: Discussionmentioning

confidence: 99%

Stem cell transplantation from identical twins in patients with myelodysplastic syndromes

Brand

Biezen

Bron

et al. 2004

“…9 Various twin transplant studies suggest that development of GVHD is likely to be a direct consequence of conditioning since the peripheral regulatory mechanism is suppressed by the high-dose chemotherapy given before stem cell transplantation, allowing expansion of autoreactive effector T cells during hematopoietic recovery and leading to selfreactivation following syngeneic BMT. 10,11 Moreover, as in allogeneic BMT, viruses also seem to influence the onset of GVHD after syngeneic grafting. Several studies have shown a correlation between viral infection and GVHD-like symptoms.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal bone marrow transplantation between brother and sister

Rana

Caniglia

et al. 2002

Summary:A child with AML underwent allogeneic BMT from an HLA-identical sister donor. Prompt and stable trilineage engraftment occurred and after few months he returned to a normal life. Eight years later a primary NHL of bone developed in his sister. A partial remission was obtained by means of standard NHL treatment, but 3 months later rapid disease progression occurred with complete bone marrow invasion (ALL-L3). She was treated with a leukemia relapse protocol, obtaining a second partial remission. Unpurged bone marrow harvested from the brother, transplanted for AML 8 years earlier, was infused after conditioning with TBI and thiothepa. No GVHD prophylaxis was given. Neutrophil engraftment occurred by 14 days and platelet engraftment by 20 days after BMT. No acute GVHD was observed, but unexpectedly she developed skin and liver GVHD-like symptoms 80 days after BMT. Since the liver biopsy was suggestive of liver GVHD and in the absence of any other evidence as a possible cause of the hepatic damage, the patient started mycophenolate. Two months later serum hepatitis B markers were detectable.

“…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

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