We analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic graft-versushost disease (GVHD) were similar after PBPC and BM transplantations regardless of age at transplantation. In patients older than 20 years, chronic GVHD and overall mortality rates were similar after PBPC and BM transplantations. In patients younger than 20 years, rates of chronic GVHD (relative risk [RR] 2.82; P ‫؍‬ .002) and overall mortality (RR 2.04; P ‫؍‬ .024) were higher after transplantation of PBPCs than after transplantation of BM. In younger patients, the 5-year probabilities of overall survival were 73% and 85% after PBPC and BM transplantations, respectively. Corresponding probabilities for older patients were 52% and 64%. These data indicate that BM grafts are preferred to PBPC grafts in young patients undergoing HLAmatched sibling donor transplantation for SAA. IntroductionTransplantation of bone marrow (BM) from an HLA-matched sibling donor is an effective treatment for severe aplastic anemia (SAA) with long-term survival in excess of 80% and graft failure rates of approximately 10%. [1][2][3][4][5][6][7] Unpublished data (January 2007) from the European Group for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) suggest approximately 60% of HLA-matched sibling donor transplantations for SAA now use peripheral blood progenitor cell (PBPC) grafts. A similar switch to PBPC over BM grafts is reported in leukemia transplantations. [8][9][10] The higher rate of chronic graft-versus-host disease (GVHD) may be offset by lower relapse rates in some settings. In contrast, there is no perceived benefit of chronic GVHD for SAA. Further, few data on PBPCs for SAA are reported. [11][12][13][14][15] In a preliminary analysis from our group, PBPC grafts appeared to contribute to higher mortality. 16 Here, we report chronic GVHD and long-term overall survival rates in 134 PBPC recipients and 558 BM recipients of HLA-matched sibling donor transplants for SAA. Patients, materials, and methods PatientsData on patients undergoing their first PBPC and BM HLA-matched sibling transplantation from 1995 to 2003 were obtained from the EBMT and the Statistical Center of the CIBMTR at the Medical College of Wisconsin. Only patients who received transplants at centers that provided a minimum of 12 months of follow-up on all their surviving patients were included. The Institutional Review Board of the Medical College of Wisconsin approved this study. Informed consent was obtained in accordance with the Declaration of Helsinki. Statistical methodsThe probabilities of hematopoietic recovery (neutrophil count Ն 0.5 ϫ 10 9 /L for 3 consecutive days and platelet count Ն 20 ϫ 10 9 /L for 7 days, unsupported) and acute and chronic GVHD were calculated using the cum...

Allogeneic PBSC results in faster neutrophil and platelet engraftment and a higher incidence of chronic GVHD than BM. However, acute GVHD, TRM, relapse, survival, and LFS were similar in patients receiving PBSCs versus BM.

Summary:We noted a significant decline in the serum concentrations of citrulline of 32 haematopoietic stem cell transplant recipients following intensive myeloablative therapy during the first 3 weeks after transplantation when patients have oral mucositis, a markedly disturbed gut integrity (L/R ratio) and are most at risk of infection and other severe complications. Closer inspection of the citrulline concentrations of 12 patients confirmed that the decline did indeed correspond to the onset of oral mucositis and altered gut integrity. Since serum citrulline is a reliable biochemical marker of small bowel enterocyte mass in humans with villous-atrophy-associated diseases, it may prove a useful marker for intestinal mucosal damage induced by chemotherapy, allowing the relationship between gut mucosal damage and post-transplant complications including infections to be explored more readily. Mucositis is a manifestation of mucosal barrier injury and is the most frequent cause of morbidity associated with the myeloablative conditioning treatment used to prepare for haematopoietic stem cell transplantation (HSCT). 1 Oral mucositis is easy to recognise, whereas detection of intestinal mucosal injury relies essentially on nonspecific symptoms such as nausea, vomiting, diarrhoea and abdominal cramps, which affect almost every HSCT recipient. An alternative means of recognising gut mucosal barrier injury is required if it is to be better understood and managed. Alterations in permeability and loss of epithelial surface are features of gut injury that can be detected by sugar permeability tests which are noninvasive and generally accepted as a surrogate marker of gut damage in patients treated for cancer. 2 However, sugar permeability tests are cumbersome and wholly dependent on patient compliance. A marker of intestinal injury that could be determined in blood would be ideal, but none has been described so far. Citrulline might prove valuable in this regard since it is an end product of glutamine metabolism of small intestinal enterocytes, cells which lack the necessary cytosolic enzymes to convert the amino acid to arginine. 3 Blood concentrations of citrulline directly reflect cell mass of the small intestine since the small intestine is the principal source of the amino acid, and it is not metabolised by the liver. 4 In mice, citrulline levels were used to quantify acute small bowel epithelial damage after single-dose whole-body irradiation. 5 The high-dose chemotherapy used to prepare patients to receive an HSCT injures the small intestine by inducing crypt apoptosis, hypoplastic villous atrophy and loss of enterocytes. 6 We determined the amino-acid profiles in the serum of a cohort of 32 HSCT recipients who had participated in a prospective randomised placebo-controlled study approved by the local Ethics Committee, the aim of which was to investigate the possible benefits of parenteral nutrition (PN) supplemented with glutamine-dipeptide. As citrulline was included, we were able to relate the concentrations tempo...

Thirty-four men and 36 women (median age 43 and 45 years, respectively) underwent stem cell transplantation (SCT) for acute leukaemia in first complete remission or chronic myelogenous leukaemia in first chronic phase between 1981 and 2001 from HLA-identical siblings. The conditioning regimen included TBI and all grafts were partially depleted of T cells. Changes in quality of life (QOL), reproduction and sexuality were studied using a questionnaire, and the previously given information related to these problems was assessed. In addition, endocrine status was assessed and semen analysis was performed. After SCT, patients reported less energy (n ¼ 50) and a deterioration in the job situation (n ¼ 31). Patients experienced a negative change in sexual relations (n ¼ 41). Important problems of sexual dysfunction were vaginal dryness in women (n ¼ 19) and erectile dysfunction in men (n ¼ 16). None of the patients was fertile based on their gonadotrophin levels, sperm concentrations and reproductive outcomes. Women experienced climacteric symptoms (n ¼ 24). Quality of life was negatively influenced by these changes. One-fifth of the patients were not satisfied with the information given with regard to reproduction, premature menopause and sexual problems.

We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day -6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p = 0.001) whilst citrulline was lower (p = 0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32+/-4 versus 37+/-3, p = 0.001) whilst CRP was higher (74+/-48 versus 34+/-38, p = 0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications.

943. 9. Mitsuishi Y, Urlacher A, Mayer S, Tongio MT. DNA-RFLP studies of the 72 core cell lines selected for the Southern blot protocol. In: Histocompatibility testing 1987. (Immunology of HLA. Vol. 1.) New York: Springer, 1989; 916. 10. Long EO, Wake CT, Gorski J, Mach B. Complete sequence of an HLA-DRB chain deduced from a cDNA clone and identification of multiple non-allelic DRB chain genes. EMBO J 1983; 2: 289 11. Auffray C, Lillie JW, Korman AJ, et al. Structure and expression of HLA-DQ and -DX genes: intrallelic alternate splicing of the HLA-DQ gene and functional splicing of the HLA-DX gene using a retroviral vector. Immunogenetics 1987; 26: 63. 12. Sheldon EL, Kellogg DE, Watson R, Leverson CH, Erlich HA. Use of nonisotopic M13 probes for genetic analysis: application to HLA class II loci. Proc Natl Acad Sci USA 1986; 83: 9085 13. Roux-Dosseto M, Auffray C, Lillie W, et al. Genetic mapping of a human class II antigen B-chain cDNA to the SB region of the HLA-complex. Proc Natl Acad Sci USA 1983; 80: 6036 14. Erlich H, Stetler D, Sherg-Dong R, Saiki R. Analysis by molecular cloning of the human class II genes. Fed Proc 1984; 43: 15. 15. Terasaki PI, Bernoco D, Par MS. Microdroplet testing for HLA-A, B, and D antigens. Am J Clin Pathol 1978; 69: 103 16. Dupont B, Brown DW, Yunis EJ, Carpenter CB. HLA-D by cellular typing. In: Terasaki PI, ed. Histocompatibility testing 1980. Los Angeles: UCLA Tissue Typing Laboratory, 1980. 17. Martell RW, Oudshoorn M, May RM, Du Toit ED. Restriction fragment length polymorphism of HLA-DRw53 detected in South African blacks and individuals of mixed ancestry. Hum Immunol 1989; 26: 237. 18. Kaminski ER. How important, is histocompatibility in bone marrow transplantation? Bone Marrow Transplant 1989; 4: 439. 19. Anasetti C, Amos D, Beatty PG, et al. Effect of HLA compatibility on engraftment of bone marrow transplantations in patients with leukemia or lymphoma. N Engl J Med 1989; 320: 197. 20. AL-Daccak R, Loiseau P, Soulie A, et al. HLA-DP genotyping in HLA-A,B, and DR identical intrafamilial bone marrow trans plantation. Leukemia 1990; 4: 222. 21. Pawelec G, Ehniger G, Schmidt H, Wernet P. HLA-DP matching and graft-versus-host disease in allogenic bone marrow trans plantation. Transplantation 1986; 42: 558. 22. Oaks MK, Carmer DV. The genetics of bone marrow transplanta tion in the rat. Transplantation 1985; 39: 69. 23. Beatty PG, Clift RA, Mickelson EM, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1985; 313: 765. 24. Kaminski E, Hows J, Man S, et al. Prediction of graft versus host disease by frequency analysis of cytotoxic T cells after unrelated donor bone marrow transplantation. Transplantation 1989; 48: 608. 25. Kaminski E, Sharrock C, Hows J, et al. Frequency analysis of cytotoxic T lymphocyte precursors: possible relevance to HLAmatched unrelated donor bone marrow transplantation. Bone Marrow Transplant 1988; 3: 149. 26. Howard MR, Hows JM, Gore SM, et al. Unrelated donor marrow transplantation between 1977 and 1987 ...

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.

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