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Biomedical subjects

J A Hansen

Publications and source records attributed to J A Hansen.

At least 91 records · Page 5Linked to original sources
PubMed1997

Effects of somatotropin and salbutamol in three genotypes of finishing barrows: growth, carcass, and calorimeter criteria.

We evaluated the combined use of 0 or 4 mg/d of recombinant porcine somatotropin (pST) and 0 or 2.75 ppm salbutamol in three genotypes of growing barrows (139 d old) differing in lean and lipid accretion potential. Treatments were in a 2 x 2 x 3 factorial arrangement, and the three genotypes tested were Meishan (M, n = 32, 49 kg), Duroc x White composite (D x Wc, n = 31, 62 kg), and Meishan x White composite (M x Wc, n = 31, 64 kg) pigs. Growth performance was evaluated over 28 d for individual pigs, and 20-h feed-deprived heat production was measured before slaughter (d 34). Daily pST injection increased ADG (+70 g/d) and reduced ADFI (-.61 kg/d) across genotypes (P < .05). Salbutamol increased (P < .05) ADG in M x Wc pigs (+146 g/d) but not in M pigs (-60 g/d) or D x Wc (+80 g/d) pigs. However, M pigs had the lowest ADG and ADFI, and M x Wc pigs not treated with salbutamol grew slower than D x Wc pigs (P < .05). Carcass protein and moisture accretion were additively (P < .05) increased by pST and salbutamol for D x Wc and M x Wc pigs. Meishan pigs had increased carcass protein and moisture accretion from pST, whereas only moisture accretion was increased by salbutamol (P < .05). The longissimus muscle area and semitendinosus weight increased as the percentage of M in the genotype decreased (P < .05), and both were increased by pST or salbutamol treatment (P < .001). Leaf fat was decreased more (P < .05) in M pigs than in D x Wc or M x Wc pigs with pST injection. The similar magnitude of leaf fat reduction between D x Wc and M x Wc pigs resulted in a mean genotype difference (P < .05), and salbutamol decreased leaf fat across genotypes. Oxygen consumption and heat production were increased by pST in M pigs more than in the crossbred genotypes, but CO2 production was reduced by similar magnitudes across genotypes, and salbutamol only tended to reduce CO2 production in D x Wc pigs. In general, these data indicate that pST and salbutamol result in additive increases in carcass lean composition; however, growth rate, carcass accretion, and various organ weights may vary among genotypes with salbutamol and pST treatment.

Albuterol↗
PubMed1997

Effects of somatotropin and salbutamol in three genotypes of finishing barrows: blood hormones and metabolites and muscle characteristics.

We evaluated the effects of recombinant porcine somatotropin (pST) and the beta-adrenergic agonist salbutamol on plasam endocrine and metabolite profiles and muscle chemistry in three genotypes of growing barrows (n = 96, 139 d old). Treatments were in a 2 x 2 x 3 factorial arrangement, and main effects were pST (0 or 4 mg/d) and salbutamol (0 or 2.75 ppm); the three genotypes including purebred Meishan (M), 1/4 Duroc, 3/4 White composite (D x Wc), and 1/4 Meishan, 3/4 White composite (M x Wc). Individual pigs were injected daily with buffer or pST at 0700 and allowed ad libitum access to a corn-soybean meal diet (1.2% lysine) and water for 33 d. Plasma was obtained 4 h after injection and 3 h postprandially on d 0, 14, and 28 for determination of growth hormone (GH), insulin, IGF-I, glucose, urea N (PUN), NEFA, triglycerides, and cholesterol. Longissimus and semitendinosus samples were obtained, and protein, RNA, and DNA were quantified and loin chop shear force was measured. In general, plasma hormones and metabolites on d 14 and 28 were not affected by salbutamol in the absence of pST, although salbutamol tended to increase d 14 and 28 GH concentrations. Salbutamol lowered plasma IGF-I (d 14 and 28, P < .05), insulin (d 14, P < .01), and NEFA (d 28, P = .07) when pST was administered, although concentrations still exceeded those for control pigs. Salbutamol reduced (P < .05) IGF-I in M and M x Wc pigs, and GH was not changed in M pigs. Meishan pigs had a greater increase in glucose with pST than M x Wc or D x Wc pigs, although the effect was not consistent over time. Individual treatment with pST caused GH, insulin, IGF-I, glucose, NEFA, and triglycerides to be increased and PUN to be decreased on d 14 and 28. Cholesterol on d 14 and 28 was decreased by pST in M pigs, whereas no effects were found in the other genotypes. Muscle protein and RNA were increased by salbutamol and were consistently lowest for M pigs. Furthermore, pST did not affect muscle protein, but it increased RNA more in M pigs than in the others. Overall, pST and salbutamol seemed to act separately and by different mechanisms to alter muscle composition, but blood criteria generally representing fat metabolism (insulin, glucose, NEFA, triglycerides) were interactively affected. Meishan pigs tended to have greater changes in muscle and plasma composition with pST treatment than did M x Wc or D x Wc pigs.

Adrenergic beta-Agonists↗
PubMed1997

Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine?

One hundred three patients with leukemia, aplastic anemia, or myelodysplastic syndrome were treated by marrow transplantation from genotypically HLA-identical siblings (n = 92) or HLA haploidentical family members differing for one HLA antigen on the nonshared haplotype (n = 11). To prevent graft-vs.-host disease (GVHD), they were administered postgrafting immunosuppression with a short course of intermittent methotrexate with daily cyclosporine for no more than 11 days. Customarily, we have given cyclosporine for 180 days after transplant. In the current study, we asked whether cyclosporine could be stopped earlier without affecting the risk of chronic GVHD. By day 60, patients who never had acute GVHD, or whose acute GVHD had resolved, were randomized to have cyclosporine stopped (n = 52) or continued for the usual 180 days (n = 51). Results were analyzed with a median follow-up of 9.3 years after transplant, and showed that patients in whom cyclosporine was discontinued on day 60 had a significantly more rapid onset (p = 0.001), but not a significantly higher overall incidence of chronic GVHD than those in whom the drug was stopped on day 180 (43 vs. 54%; p = 0.26). Transplant-related mortality was comparable among patients without preceding acute GVHD, regardless of when cyclosporine was discontinued (11% for both study arms). However, transplant-related mortality appeared to increase among patients with preceding acute GVHD in whom cyclosporine was stopped by day 60 (38 vs. 17%). Results suggest that cyclosporine can safely be discontinued early in patients who never had evidence of acute GVHD, while those with preceding acute GVHD would benefit from a longer course of the drug. Because of the relatively small sample sizes, these results would best be treated as promising preliminary findings that should be confirmed in larger randomized studies.

Adult↗
PubMed1996

Definition of HLA-DQ as a transplantation antigen.

Recent studies have demonstrated the importance of recipient HLA-DRB1 allele disparity in the development of acute graft-versus-host disease (GVHD) after unrelated donor marrow transplantation. The role of HLA-DQB1 allele disparity in this clinical setting is unknown. To elucidate the biological importance of HLA-DQB1, we conducted a retrospective analysis of 449 HLA-A, -B, and -DR serologically matched unrelated donor transplants. Molecular typing of HLA-DRB1 and HLA-DQB1 alleles revealed 335 DRB1 and DQB1 matched pairs; 41 DRB1 matched and DQB1 mismatched pairs; 48 DRB1 mismatched and DQB1 matched pairs; and 25 DRB1 and DQB1 mismatched pairs. The conditional probabilities of grades III-IV acute GVHD were 0.42, 0.61, 0.55, and 0.71, respectively. The relative risk of acute GVHD associated with a single locus HLA-DQB1 mismatch was 1.8 (1.1, 2.7; P = 0.01), and the risk associated with any HLA-DQB1 and/or HLA-DRB1 mismatch was 1.6 (1.2, 2.2; P = 0.003). These results provide evidence that HLA-DQ is a transplant antigen and suggest that evaluation of both HLA-DQB1 and HLA-DRB1 is necessary in selecting potential donors.

Adolescent↗
PubMed1996

FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors.

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus-host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno-occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan-Meier estimates of disease-free survival at 2 years for good-risk, poor-risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.

Adolescent↗
PubMed1996

Induction of apoptosis by anti-CD3 epsilon F(ab')2 in antigen receptor transgenic murine T cells activated by specific peptide.

Peripheral T cell tolerance can be achieved through deletion of mature CD4+ cells activated by high dose Ag. We tested whether apoptosis of peripheral CD4+ cells could be induced by a stimulatory dose of Ag plus a soluble ligand to the nonpolymorphic epsilon-chain of the TCR-associated CD3 complex. CD4+ T cells from the DO10 mouse express a transgenic TCR-alphabeta specific for OVA peptide 323-339 presented by I-A(d). OVA alone induced clonal activation and expansion of peripheral CD4+/TCR transgene+ cells. Simultaneous exposure to specific Ag plus soluble anti-CD3 Fos, a nonmitogenic anti-CD3epsilon genetically engineered F(ab')2-like Ab, blocked expansion and induced death of CD4+/TCR transgene+ cells, but not CD4+/TCR transgene- T cells. In contrast, a mitogenic anti-CD3epsilon Ab induced polyclonal activation and nonselective T cell death. Sequential stimulation by Ag followed by anti-CD3 Fos also induced death of TCR transgene+ cells, whereas stimulation by anti-CD3 Fos followed by Ag did not affect cell viability or function. Anti-CD3 Fos-induced death was associated with DNA fragmentation characteristic of apoptosis, was facilitated by IL-2, and was initiated by stimulation during the S-G2 phases of the cell cycle. Anti-CD3 Fos could induce deletion of Ag-activated T cells by apoptosis in vivo. Thus, a soluble, non-Fc-binding anti-CD3 Ab can induce programmed cell death of Ag-activated peripheral CD4+ T cells by CD3epsilon cross-linking during S or G2. Peripheral T cell deletion by activation-driven apoptosis is under cell cycle control and can be exploited to achieve selective immunosuppression by nonmitogenic anti-CD3epsilon Abs.

Amino Acid Sequence↗
PubMed1996

Alloantigen presenting function of normal human CD34+ hematopoietic cells.

The identification of the CD34 molecule, expressed almost exclusively on human hematopoietic stem cells and committed progenitors, and the development of CD34-specific monoclonal antibodies have made procurement of relatively pure populations of CD34+ marrow cells for autologous transplantation feasible. Characterization of the immunogenicity of CD34+ marrow cells may facilitate the design of successful strategies to use these cells for allogeneic transplantation. CD34+ marrow cells from normal volunteers were enriched to greater than 98% purity by immunoaffinity chromatography on column followed by fluorescence-activated cell sorting. Purified CD34+ cells were tested for expression of HLA-DR and other accessory molecules, and function in hematopoietic colony growth and mixed leukocyte culture (MLC) assays. Greater than 95% CD34+ cells were positive for HLA-DR and 74% +/- 10% were highly positive for CD18, the common beta-chain of a leukointegrin family. CD34+/CD18- cells were small, agranular lymphocytes which contained the majority of precursors for colony-forming cells detected in long-term cultures. They produced almost no stimulation of purified T cells from HLA-DR-incompatible individuals in bulk MLC or in limiting dilution assay. In contrast, CD34+/CD18+ cells were large, were enriched for cells forming mixed colonies in short- but not long-term assays, and were capable of stimulating allogeneic T cells. CD86, a natural ligand for the T-cell activation molecule CD28, was coexpressed with CD18 in 6% +/- 3% of CD34+ cells. CD34+/CD86+ cells, but not CD34+/CD86- cells, exhibited strong alloantigen presenting function. Thus, pluripotent hematopoietic activity and alloantigen presenting function are attributes of distinct subsets of CD34+ marrow cells. CD34+/CD18- or CD34+/CD86- cells may be more effective than either the whole CD34+ population or unseparated marrow in engrafting allogeneic recipients and may also facilitate induction of tolerance.

Adult↗
PubMed1996

Evaluation of a CD5-specific immunotoxin for treatment of acute graft-versus-host disease after allogeneic marrow transplantation.

Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme. CD5-Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients were treated concomitantly with a standard regimen of methylprednisolone. At the time of entry on study, 94% of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was less in the CD5 group than in the placebo group. At 4 weeks, 40% of patients assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P = .019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared with 38% in the placebo group (P = .36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in the control group (P = .35). Survival at 1 year after treatment was 49% in the CD5 group and 45% in the control group (P = .68). Side effects required close monitoring and appropriate adjustment of treatment. The combined administration of a CD5-specific immunotoxin and glucocorticoids controls GVHD manifestations more effectively than treatment with glucocorticoids alone during the first 5 weeks after starting treatment. Use of this immunotoxin does not result in any long-term clinical benefit for patients with acute GVHD.

Acute Disease↗
PubMed1996

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors.

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3-year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.

Actuarial Analysis↗
PubMed1996

The Dai minority population of southwest China: heterogeneity of DR2-associated HLA-DRB1,DRB5,DQA1, and DQB1 haplotypes.

HLA-DR2 is the most common DR specificity (60.3%) identified in the Dai minority population of Xishuangbanna, Yunna Province, China. We characterized the DRB1, DRB5, DQA1, and DQB1 alleles of 44 unrelated DR2-positive individuals, 11 of whom (15%) were DR2 homozygous. Four DRB1 and four DRB5 alleles encoding DR2 were identified in this population. The most frequent DR2-associated DRB1 alleles were *1602 (gf = 0.164) and *1502 (gf = 0.151). DRB1*1501 (gf = 0.048) and a new allele designated DRB1*1504 (gf = 0.014) were also detected, but *1601 and *1503 were absent. The most frequent DR2-associated DRB5 alleles were *0101 (gf = 0.233) and *0102 (gf = 0.110). Nine different DR2-associated DR/DQ haplotypes were identified. The two most common DR2 haplotypes were DRB1*1602, DRB5*0101, DQA1*0102, DQB1*0502 (hf = 0.142) and DRB1*1502, DRB5*0102, DQA1*0101, DQB1*0501 (hf = 0.075). The new DRB1*1504 allele was found on a single haplotype: DRB1*1504, DRB5*0101, DQA1*0102, DQB1*0502 (hf = 0.017). The Dw2, Dw12, Dw21, and Dw22 haplotypes, present in many other Asian and Mongoloid populations, were not identified in this unique group. However, the Dai minority population is characterized by a relatively large number of diverse DR2 haplotypes and a new DRB1 allele encoding DR2.

China↗
PubMed1996

Unrelated donor marrow transplantation for myelodysplasia (MDS) and MDS-related acute myeloid leukaemia.

Allogeneic marrow transplantation using related marrow donors for myelodysplasia (MDS) and acute myeloid leukaemia (AML) arising from MDS results in 35-56% actuarial disease-free survival. Because the use of unrelated donors has not been well-characterized, we report on the outcome of 52 patients with MDS or MDS-related AML consecutively treated between 1987 and 1993 with unrelated donor marrow transplantation. The median age was 33 (range 1-53) years. 33 patients received chemotherapy and total body irradiation and the remainder busulfan and cyclophosphamide. The donors were phenotypically identical at the HLA-A, B and Dw/DRB1 loci in 34 cases and mismatched for one HLA locus in 17 cases and two loci in one case. Marrow was non-T-cell depleted and methotrexate with cyclosporine or FK506 was used for postgrafting immunosuppression. The 2-year disease-free survival, relapse, and non-relapse mortality rates were 38%, 28% and 48%, respectively. One patient who relapsed survives disease-free after withdrawal of immunosuppressive therapy. 16/19 survivors have a performance status of 90-100%. Patients with MDS in transformation or with AML had a significantly higher risk of relapse than patients with less advanced disease (P = 0.0014). Increased non-relapse mortality was significantly associated with higher age, longer disease duration before transplant, lower neutrophil count on admission and, unexpectedly, being seronegative for cytomegalovirus. We conclude that the outcome with transplantation using unrelated donors is similar to reported results using related donors and that a meaningful proportion of eligible patients with an otherwise incurable disease may be cured with this treatment. However, mortality from the transplant procedure is high and future studies should focus on reducing toxicity.

Acute Disease↗
PubMed1996

Evaluation of the mixed lymphocyte culture (MLC) assay as a method for selecting unrelated donors for marrow transplantation.

The utility of the MLC assay as a test of HLA-D region matching and predictor of graft-versus-host disease (GvHD) was evaluated in 435 patients receiving marrow grafts from unrelated donors. Donors and recipients were phenotyped for HLA-A, B and DR antigens by serology, tested in MLC, and retrospectively genotyped for DRB1, B3, B4, B5, DQB1 and DPB1 alleles by PCR/SSOP. Of the 244 HLA-A, B, DR-identical donor-recipient pairs with valuable MLC and DRB1 typing results available, 208 were matched for HLA-A, B and DRB1, while 36 were matched for HLA-A and B and mismatched for a DRB1 allele. Donor anti-recipient relative responses (RR) in MLC, corresponding to the GvHD vector in marrow transplantation, ranged from 7.2 to 100%, with a median of 4.0%. A comparison of reactivity in MLC between pairs matched versus mismatched for DRB1 alleles showed a significant overlap in the distribution of RRs. Using optimally-defined RR cutoffs of 4 and 16%, no correlation between MLC results and risk of developing clinically significant grades III-IV GvHD (p=0.6 and 0.5, respectively) was found when the contribution of DRB1 mismatch was accounted for. Matching for DRB1 alleles, in contrast, was a better predictor of clinically significant GvHD, with DRB1-matched transplant recipients less likely to develop grades III-IV GvHD than DRB1-mismatched recipients (p=0.14). Among the 208 patients and donors matched for DRB1 alleles, the MLC, although reactive (RR > 4.0%) in 45% of cases, did not predict GvHD. Overall, these results underscore the limitations in using the MLC to predict DRB1 matching or risk of clinically significant GvHD among patients receiving unrelated marrow grafts. The availability of DRB1 allele matching by sequence-specific oligonucleotide probes (SSOP) or by direct sequencing provides a method for donor matching that is rapid, precise and superior to the MLC for predicting clinically relevant outcome.

Acute Disease↗
PubMed1996

Six new DR52-associated DRB1 alleles, three of DR8, two of DR11, and one of DR6, reflect a variety of mechanisms which generate polymorphism in the MHC.

We have sequenced DNA from six new DR52-associated DRB1 alleles initially detected by PCR/SSOP analysis. Three DR8 associated alleles differed from previously known alleles by single nucleotide substitutions. DRB1*0807 and DRB1*0811 both vary from DRB1*08021 at codon 57 resulting in two different amino acids at this residue. DRB1*0807 was identified in samples of Brazilian origin while *0811 was identified among samples from the Tlingit Native American population of Southeast Alaska. DRB1*0814, identified in a family of Chinese origin, differed from DRB1*08032 at codon 12 at both the nucleotide and the amino acid level. In addition, two alleles of DR11, DRB1*1113 and *1119, were each detected in Caucasian individuals. DRB1*1113 differs from other DR11 alleles at codons 37, 67, 70 and 74, while DRB1*1119 differs from *1101 by a single nucleotide substitution at codon 67. Finally, DRB1*1418 was detected in a sample from an Asian or Pacific Islander and shares sequences with several other DR52-associated DRB1 alleles. These six DRB1 alleles appear to have been generated by either gene conversion events, DRB1*1113 and *1418, or by point mutations, DRB1*0814, *0807, *0811 and *1119, although the single nucleotide substitutions found in the latter three alleles are also present in at least one other DRB1 allele and, therefore, could have been the product of gene conversions.

Base Sequence↗
PubMed1996

A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery.

To determine whether intravenous immunoglobulin (IVIg) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection, chronic graft-vs.-host disease (GVHD), and obliterative bronchiolitis after marrow transplantation, patients were assigned randomly to receive either IVIg (500 mg/kg/month) or no IVIg prophylaxis. Participants were registered before transplantation, and 250 patients (123 IVIg and 127 control) were evaluable for events after day 100. The two groups were balanced for age, marrow source, cytomegalovirus (CMV) seropositivity, pretransplantation conditioning, and prophylaxis for infection and GVHD. Between days 100 and 365 posttransplantation, the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls (p = not significant). During the same period, the incidence of localized infection was marginally higher in control patients than in IVIg recipients (0.44 vs. 0.24, respectively; relative risk [RR] 1.46, p < 0.07). Administration of IVIg prophylaxis had no effect on survival, the incidence of obliterative bronchiolitis, severity of airflow obstruction, or the incidence or mortality of chronic GVHD. After discontinuing IVIg prophylaxis at day 360, subsequent recovery of endogeneous humoral immunity was impaired (serum IgG1 and IgA levels were significantly lower than controls at day 730), and total infections were less common in the second year in control patients than in former IVIg recipients (0.12 vs 0.19, respectively; RR 0.61, p = 0.03). We conclude that in the absence of hypogammaglobulinemia, monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation.

Adolescent↗
PubMed1995

Unrelated donor marrow transplantation in children.

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acute or chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome.

Adolescent↗
PubMed1995

Detection of maternal cells in human umbilical cord blood using fluorescence in situ hybridization.

Cord blood is a potential source of hematopoietic stem cells for transplantation and is being used on a growing number of patients. However, there are concerns that cord blood might be contaminated with maternal cells that could lead to graft-versus-host disease. To ascertain the extent to which maternal cell contamination of cord blood occurs, we examined 49 cord blood samples from male babies for maternal cells by fluorescence in situ hybridization using probes to the X and Y chromosomes. A minimum of 1,000 nuclei were scored from each sample, and maternal cells were found in 7 of the 49 cord bloods, at levels ranging from 0.04% to 1.0%. In addition, in 39 and 27 of the cord blood samples, respectively, we examined the CD8+ and CD34+ cell populations for maternal cells. Maternal cells were found in 5 of the 39 CD8 fractions and in 1 of the 27 CD34 fractions, at levels similar to that found in the unfractionated cord blood. In sum, maternal cells were found in either the unseparated mononuclear fraction or the CD8 or CD34 fractions in 10 of the 49 cord blood samples (20%). These results show that maternal cells are present in a substantial number of cord bloods, and that some of these maternal cells are T cells.

Antigens, CD↗