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The outcome of matched unrelated donor bone marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host disease prophylaxis regimen of cyclosporine, methotrexate, and prednisone.

Graft-versus-host disease (GVHD) is a major obstacle to successful bone marrow transplantation (BMT) from matched unrelated donor (MUD). Currently available HLA-A, -B, and -DR serologic testing may not be sensitive enough to detect clinically relevant donor/recipient (D/R) nonidentity. Better HLA matching of D/R pairs using molecular typing for class II antigens in combination with intensive GVHD prophylaxis may potentially reduce the incidence of GVHD and lead to an improved outcome of MUD transplantation. Between July 1991 and August 1993, thirty consecutive patients with hematologic malignancies underwent MUD transplantation from donors who were identical for HLA -A, -B, and -DR by serologic typing. Twenty-five D/R pairs were matched for DRB and DQB by molecular typing (restriction fragment-length polymorphism and sequence-specific oligonucleotide probe hybridization analyses), whereas five were allele mismatched at either DRB or DQB. All patients also received GVHD prophylaxis with the combination of cyclosporine (CSA), methotrexate (MTX), and prednisone (PSE). The median age was 35 years (range, 15 to 50). The diagnoses were: chronic myelogenous leukemia (CML) in chronic phase (CP) (16), CML in more than CP (3), acute leukemia in more than first complete remission (CR) (8), acute leukemia in first CR (1), and advanced high-grade lymphoma (2). The preparative regimen consisted of 1,320 cGy fractionated total body irradiation (FTBI) and 60 mg/kg cyclophosphamide (CY) daily for 2 days in 17 good-risk patients (CML/CP and acute leukemia first CR); and 1,320 cGy FTBI in combination with 60 mg/kg etoposide and 20 to 60 mg/kg CY in 13 patients with advanced leukemia and lymphoma. All patients received CSA, PSE, and MTX on days 1, 3, 6 for GVHD prophylaxis, and 10 patients also received day +11 MTX. All patients engrafted except one who died early of regimen-related toxicity. The incidence of grade III or IV acute GVHD was 24% (95% confidence interval [CI], 10% to 44%) and that of extensive chronic GVHD was 65% (95% CI, 43% to 84%). At a median follow-up of 13.6 months, 57% of the patients are alive in remission with a median Karnofsky performance status of 90%. The cumulative probability of 2-year disease-free survival for all patients was 53% (95%) CI, 33% to 71%); for good-risk patients, 71% (95% CI, 46% to 87%) and for the poor-risk group, 34% (95% CI, 13% to 64%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Donor selection, testing, and inactivation of the HIV virus in freeze-dried bone allografts.

This article is a comprehensive review of the safety of currently used freeze-dried bone allografts. The development of exclusionary criteria for donor procurement is discussed along with the steps taken in processing. The processing includes harvesting in a sterile manner, repeated washings, immersion in ethanol, freezing in liquid nitrogen, freeze-drying, demineralization, and vacuum sealing. The statistical data of laboratory testing for the HIV virus is presented, and the advantages and disadvantages of the ELISA and the PCR tests are outlined. There are four known cases of HIV transmission from bone allograft donors, and the circumstances of these four transmissions are discussed. An overview of hepatitis and other infectious diseases in bone allografts completes the review. The learning objective of this article is to update reader knowledge of measures taken to ensure safety in the utilization of DFDB allografts.

Bone Banks↗

Donor selection limits use of living-related liver transplantation.

The purpose of this investigation was to assess the applicability of living-related liver transplantation in an established regional transplant program by determining the frequency of acceptable living donors from an unselected population of pediatric transplant candidates and identify specific factors limiting application of this technique. During the period May 1992 to May 1994, all children accepted as transplant candidates at the University of California-San Francisco were evaluated for potential living-related liver transplantation. Indications for transplantation and patient demographics represented the spectrum anticipated at a regional center. Donor evaluation was performed using a three-phase evaluation process we have previously reported. Retrospective analysis identified 75 potential donors for 38 pediatric candidates (age range, 17 days to 14.5 years; mean, 5.1 years). Twenty-three percent of potential donors declined evaluation. Of the 75 potential donors, only 10 (13%) were found to be acceptable for donation. The leading causes for donor declination were significant medical history (23%), ABO blood group incompatibility (23%), and psychosocial history (20%). Of the 38 recipient candidates, 9 (23%) were offered living-donor transplantation. Five patients have received living-donor transplantation, and 4 patients await the procedure when medical indications exist. Seventy-seven percent of recipient candidates received or are awaiting cadaveric transplantation. These results suggest that current donor criteria markedly limit the application of living-related liver transplantation.

Adolescent↗

Donor selection process for allogeneic hematopoietic stem cell transplantation at the university hospital of Düsseldorf (1997-1998).

BACKGROUND: Transplantation of hematopoietic stem cells (HSC) is an effective treatment for a number of patients with life-threatening hematologic diseases. HSC donors can be found in the family of the patient or in registries of unrelated donors. In the present study, the search procedure within the last two years for an allogeneic HSC donor at the University of Düsseldorf is analyzed. PATIENTS AND METHODS: During 1997 and 1998, an early search for a related HSC donor in the family was performed for 70 high risk pediatric patients. During the same period, the search for an unrelated HSC donor for 116 adult and pediatric patients was performed. Low resolution HLA-A and -B typing was performed by serology in combination with DNA-typing. High resolution typing of HLA-A, -B and -C was carried out by DNA-sequencing. Low resolution HLA-DRB- und HLA-DQB1-typing was done solely by DNA-typing and high resolution typing of these genes was performed by DNA-sequencing. MAIN RESULTS: For 51 of 70 high risk pediatric patients (73%), no family donor could be defined, 16 of 70 patients (23%) had a genotypically identical sibling and for three of 70 patients (4%) an HLA-acceptable donor in the extended family could be identified. The search for an unrelated HSC donor was successful in 74% of the adult and pediatric patients lacking such a family donor. Most noteworthy, nearly all of the HLA-acceptable donors were identified from that group of donors in the registries, which were not only HLA-A and HLA-B, but also HLA-DR pretyped. CONCLUSION: These data show, that a growing number of pediatric patients with high risk leukemia need an unrelated HSC donor and that HLA-ABDR-pretyped registries present the optimal prerequisite to identify an HSC donor for most of the patients. In addition, 25% of the patients with no family or unrelated HSC donor require HSC transplants from alternative donors like unrelated Cord Blood (CB) from high quality cord blood banks.

Adult↗

Donor selection for single and double lung transplantation. Chest size matching and other factors influencing posttransplantation vital capacity.

In six single lung transplant (SLT) and six double lung transplant (DLT) recipients, the relationships of the recipient's posttransplantation vital capacity (posttx VCR) to the recipient's predicted normal vital capacity (pred VCR) and the donor's predicted normal vital capacity (pred VCD) were investigated. After left SLT the left posttx VCR was correlated with the left predicted VCD (r = 0.83; p less than 0.05); however, no correlation was found between these after DLT. In contrast, there was a tendency toward correlation between the posttx VCR and the predicted VCR after DLT (r = 0.75; p less than 0.1), but no such trend was apparent after SLT. These results suggest that posttx VCR depends primarily on predicted VCD after SLT and on pred VCR after DLT. Therefore, in donor-recipient size matching for lung transplantation a donor with a pred VCD greater than the pred VCR should be chosen for a left SLT recipient, whereas a donor with a pred VCD near the pred VCR would be suitable for a DLT recipient.

Adult↗