Jerome L. Gottschall

Successful Allogeneic Transplantation of T-Cell–Depleted Bone Marrow from Closely HLA-Matched Unrelated Donors

We describe a four-year experience with bone marrow transplantation involving closely HLA-matched unrelated donors and 55 consecutive patients with hematologic disease who were seven months to 48.6 years old (median, 18 years). An intensive pretransplantation conditioning regimen and graft-versus-host disease (GVHD) prophylaxis with CD3-directed T-cell depletion and cyclosporine were employed. Durable engraftment was achieved in 50 of 53 patients who could be evaluated (94 percent; 95 percent confidence interval, 83 to 98 percent). Acute GVHD of Grade II to IV developed in 46 percent of the patients (confidence interval, 27 to 66 percent). The incidence and severity of acute GVHD were increased in recipients of HLA-mismatched marrow as compared with recipients of phenotypically matched marrow (incidence of 53 percent [confidence interval, 37 to 68 percent] vs. 17 percent [confidence interval, 5 to 45 percent]; P less than 0.05). Extensive chronic GVHD and deaths not due to relapse also tended to be more frequent when HLA-mismatched marrow was used, but not significantly so. With a median follow-up of more than 19 months (range, greater than 9 to greater than 39), the actuarial disease-free survival of transplant recipients with leukemia and a relatively good prognosis (acute leukemia in first remission and chronic myelogenous leukemia in chronic phase) was 48 percent (confidence interval, 24 to 73 percent), and that of recipients with more aggressive leukemia was 32 percent (confidence interval, 18 to 51 percent); the actuarial survival of recipients with non-neoplastic disease was 63 percent (confidence interval, 31 to 86 percent). We conclude that marrow transplantation with closely HLA-matched unrelated donors can be effective treatment for neoplastic and non-neoplastic diseases. Although transplants from phenotypically HLA-matched unrelated donors appear to be most effective, transplants with limited HLA disparity can also be successful in some patients.

The effect of previous pregnancy and transfusion on HLA alloimmunization in blood donors: implications for a transfusion-related acute lung injury risk reduction strategy

BACKGROUND: Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion‐related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening plateletpheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined.

One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.

BACKGROUND: Drug‐induced immune hemolytic anemia (DIIHA) is an uncommon finding characterized by a sudden decrease in hemoglobin after treatment with the putative drug. The full range of drugs causing DIIHA and the initial serologic presentation are not fully appreciated. This work identifies additional drugs associated with DIIHA and offers additional insights about diagnosis.

Thrombotic thrombocytopenic purpura: early and late responders.

Thrombotic thrombocytopenic purpura (TTP) is characterized by micro‐angiopathic hemolytic anemia (MAHA), thrombocytopenia, neurological symptoms, renal involvement, and fever. We describe our experience in 70 serially encountered TTP patients in the last decade who were treated with a standard therapeutic plasma exchange (TPE) protocol. Seventy percent of the patients were females. The median age of the patients was 43 years (range: 8–80). Sixty patients (85.7%) had a complete response to TPE therapy. This represented 91% of 66 who received at least one TPE. Ten patients died, two patients died before and two during the first plasma exchange. The median number of TPEs performed was nine (range: 1–85). Thirty‐five (58%) out of 60 responded to 3–9 TPEs, and 25 (42%) required 10–34 TPEs for the response. The median total plasma volume exchanged was 28 liters (range: 2.7–250 L) and the mean plasma volumes exchanged during each prodcedure was 3.2 (SD ± 1.09 L). The patients were classified into early responders (ER) and late responders (LR). ERs had a mean platelet count of 180 × 109/L by Day 5, mean LDH of 643 IU/L by Day 7, and required median of seven TPEs. LRs had a mean platelet count of 122 × 109/L by Day 5, mean LDH of 885 IU/L by Day 7, and required median of 19 TPEs (P = 0.001). The platelet counts were significantly higher (P = 0.01–0.03) in ERs on Days 1, 3, and 5 as compared to LRs but the LDH did not differ significantly. Seventy‐seven percent of LRs had exacerbation of TTP and 18% had relapse as compared to 7% each in ERs. Thirteen patients were in coma/semicoma at presentation. Out of these, six died, making coma a bad prognostic indicator. Five of the seven survivors in coma had received two single‐plasma volume exchanges on Day 1. In conclusion, 91% of TTP patients had an excellent response to plasma exchange therapy with FFP. Coma/semicoma appears to be a bad prognostic indicator. LRs needed prolonged treatment with a greater number of patients experiencing exacerbation and relapse of TTP as compared to ERs. Am. J. Hematol. 54:102–107, 1997

Detecting fetomaternal hemorrhage: a comparison of five methods

Appropriate postpartum administration of Rh immune globulin relies on sensitive detection and accurate quantitation of fetomaternal hemorrhage (FMH). Recently, the microscopic Du test (micro Du) enhanced with polyethylene glycol (PEG Du) and flow cytometry (FC) have been advocated for this purpose. Three qualitative methods (micro Du, rosette test, and PEG Du) and two quantitative methods (acid elution and FC) for assessing FMH were evaluated with particular attention given to PEG Du and FC. In vitro studies comprised 10 series of dilutions of D+ cord cells in D− adult cells to yield D+ cell concentrations of 0.06, 0.12, 0.25, 0.50, 0.75, 1.0, and 2.0 percent. Additionally, 26 postpartum samples were tested. Of the qualitative techniques, the micro Du test was the least sensitive with 20 percent false‐negative results occurring at 0.5 percent fetal cells. The PEG Du test was only slightly more sensitive and offered no clinical advantage. The rosette test was the most sensitive, consistently detecting fetal cells at concentrations of 0.25 percent or greater. FC and acid elution showed similar results, with good correlation obtained between measured and expected quantities of fetal cells (r = 0.99 and 0.96, respectively). One of 26 postpartum samples was positive by all screening techniques; acid elution and FC detected 0.3‐percent concentrations of fetal cells and 0.17‐percent concentrations of D+ cells, respectively. Although acid elution is a more commonly used method for quantitating FMH, FC offers an acceptable alternative that is capable of analyzing large numbers of cells with objectivity and reproducibility.

Making thawed universal donor plasma available rapidly for massively bleeding trauma patients: experience from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial

The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request.

Evaluation and comparison of coagulation factor activity in fresh-frozen plasma and 24-hour plasma at thaw and after 120 hours of 1 to 6°C storage.

BACKGROUND: Current transfusion‐related acute lung injury reduction strategies include avoiding transfusion of plasma products collected from female donors or female donors that have been pregnant to reduce transfusion of plasma‐containing HLA antibodies. Such a policy considerably decreases the number of donors available for generation of fresh‐frozen plasma (FFP). To increase the supply of FFP, substitution of 24‐hour plasma (FP24) and thawed plasma (TP) derived from either FFP or FP24 may be viable substitutes. To justify such a policy the coagulation factor content of FFP, FP24, and TP derived from both product types was assessed.

Importance of white blood cells in platelet storage.

Abstract. Platelet concentrates from 290 healthy donors collected in CPD anticoagulant and PL‐146 polyvinylchloride containers were stored for 72 h at 22±0.5°C under standard conditions to investigate variables affecting the quality of stored platelets. In addition to the expected inverse relationship between pH and platelet count (p < 0.001), a significant inverse correlation between pH and white blood cell count (WBC) was also noted (p < 0.01). Platelets from female donors developed a lower pH than those from male donors; this difference could not be accounted for by any of the variables analyzed other than sex. To investigate the relationship between WBC and pH further, 15 units of platelet‐rich plasma (PRP) were depleted of WBCs by slow centrifugation prior to being stored for 3 days. This resulted in a mean loss of 10% of the platelets and 75% of the WBCs. The average post‐storage pH of the 15 WBC‐poor concentrates (7.06 ± 0.02) was significantly higher than that of routinely prepared concentrates containing the same number of platelets (6.54 ± 0.43) (p < 0.001). Production of lactic acid and consumption of glucose was markedly diminished in leukocyte‐poor concentrates. These data suggest that WBCs significantly affect the metabolic activity of platelet concentrates and that the quality of stored platelets can be improved by reducing the number of contaminating leukocytes. Measurement of leukocytes may be important in quality control of platelet concentrates.

Prevalence of HLA antibodies in remotely transfused or alloexposed volunteer blood donors

BACKGROUND: HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion‐related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized.

Studies of the minimum temperature at which human platelets can be stored with full maintenance of viability.

Platelet concentrates from normal donors were stored for 3 days under identical conditions except for the temperature of storage, which was maintained at 21 ± 0.5, 19.5 ± 0.5, or 18 ± 0.5°C. Immediate posttransfusion recovery of the stored platelets determined by 51Cr labeling averaged 47, 47, and 48 percent after storage at 21, 19.5, and 18°C, respectively (differences not significant). Mean life span of the transfused platelets, however, was 8.12, 5.21, and 1.85 days at 21, 19.5, and 18°C, respectively. The difference between mean life span following storage at 21°C was significantly different from that after storage at 18°C (p < 0.03). Reduction in viability after storage at the lower temperature correlated with the reduction in the number of discoid platelets. These findings indicate that platelet viability is compromised after storage for 3 days at 18° C and, possibly, at 19.5° C, and illustrate the need for quality control of temperature in short‐term platelet storage.