Ronald A. Yankee

Selection of Unrelated Compatible Platelet Donors by Lymphocyte HL-A Matching

Abstract Thrombocytopenic patients who are refractory to transfusions of platelets obtained from random donors will respond to platelets from HL-A-identical siblings. The efficacy of using HL-A lymphocyte typing to select unrelated compatible platelet donors, however, has not been well documented. In this study, three patients who were not responding to random donor platelets were transfused with platelets obtained from selected unrelated persons matched for HL-A. The median response in circulating platelets (increment times body-surface area per unit) measured at 20 hours was 11.2, 9.1 and 17.0 (X 103) as compared to 0, 0 and 2.2 (X 103), respectively, to nonmatched platelets. These observations indicate that alloimmunization in multi-transfused patients is primarily due to HL-A antigens and that lymphocyte HL-A typing can be used to select unrelated compatible platelet donors for refractory patients.

Platelet Transfusions From HL-A Compatible Unrelated Donors to Alloimmunized Patients

Abstract Patients needing long-term platelet transfusion support become alloimmunized to transplantation (HL-A) antigens present in random-donor blood products, which results in refractoriness to p...

HL-A antigens and disease: Acute lymphocytic leukemia

50 Caucasian children with acute lymphocytic leukemia (ALL) and 219 members of their families have been genotyped for 15 antigens of the HL-A system. The antigen and gene frequencies for HL-A2 were significantly higher in the patient population than in a 200 member normal Caucasian panel. No other antigen frequencies were significantly elevated. All antigens typed for were found in the patients. No antigen gain or loss was detected in the leukemic cells.

Cryopreserved autologous marrow infusion following high dose cancer chemotherapy

Abstract Seventeen patients with advanced malignancies received escalating doses of chemotherapy with adriamycin and cyclophosphamide. Sixty-five per cent of the courses produced circulating granulocyte counts of 500 cells/mm3 or less. Febrile episodes occurred in only 15% of courses and were seen only with doses of chemotherapy that produced granulocyte nadirs of less than 200 cells/mm3. There were no episodes of septicaemia. Ten of the 17 patients received an intensive dose followed by reinfusion of cryopreserved, autologous bone marrow. In 5 of these patients, recovery to 500 granulocytes/mm3 was more rapid following the intensive, marrow-supported course by comparison with the prior, less intensive, unsupported course. We conclude that higher doses of adriamycin and cyclophosphamide than are conventionally used can be given without serious toxicity. Autologous bone marrow reinfusion may have a role in reducing the period of drug-induced granulocytopenia, but effective storage and recovery of human bone marrow remains a major problem.

Prophylaxis of varicella in children with neoplastic disease: Comparative results with zoster immune plasma and gamma globulin

The incidence and severity of varicella following a close family contact were evaluated in children with neoplastic diseases who received prophylaxis either with commercial gamma globulin or with zoster immune plasma, as compared to patients who did not receive any prophylaxis. In the untreated group, all 14 patients developed varicella, complicated by 1 case of encephalitis and 2 cases of fatal pneumonia. In the group of 17 patients who received 0.6–1.2 ml/kg body weight of gamma globulin, 16 developed varicella, complicated by pneumonia in 2 cases, with 1 death. In the third group of 27 patients who received 10 ml/kg body weight of zoster immune plasma (ZIP), obtained from healthy adults convalescing from herpes zoster, there were only 8 cases of varicella, all very mild. Thus, prophylaxis with ZIP significantly reduced the incidence of clinical varicella (p < 0.01) and attenuated the severity of its course.

Combination chemotherapy with adriamycin-cyclophosphamide for advanced ovarian carcinoma

Combination chemotherapy with Adriamycin‐cyclophosphamide was employed after surgical treatment in 60 women with Stage III‐IV ovarian adenocarcinoma. Of 53 evaluable patients, objective response was noted in 34 of 41 (83%) without prior cytotoxic therapy but in only two of 12 (17%) who had failed a single alkylating agent or radiotherapy (P < .005). Complete response was confirmed by a negative biopsy at the site(s) of prior disease in 12 patients. Eleven of the 12 biopsy‐confirmed complete responses were achieved in patients without pretreatment palpable tumor. Twenty‐four out of 41 patients with palpable masses responded but only one was confirmed as complete. Confirmed complete responses had a median duration of 24 months, whereas the median duration of all other responses was only seven months. The median survival for patients in whom Adriamycin‐cyclophosphamide was the initial chemotherapy was 24 months. The median survival in patients with palpable tumor exceeds that of historical controls matched for age, tumor cell type, and grade (P = .05); the median survival for the confirmed complete responders has not been reached. The toxicity of this regimen was acceptable at doses of Adriamycin and cyclophosphamide of 45 mg and 500 mg/M2 body surface area, respectively. Extensive excision of tumor followed by effective combination chemotherapy offers the best current approach toward improved patient survival in advanced ovarian cancer.

Prolonged cryopreservation of human bone marrow

We tested the viability of human bone marrow stored for 40 to 42 months in the vapor phase of liquid nitrogen. A median of 2 × 1010 nucleated cells obtained from eight patients were concentrated to 1.3 × 1010 using discontinuous centrifugation. These were stored in polyolefin bags in volumes of 100 to 500 ml using 10% dimethyl sulfoxide (DMSO) as a cryoprotectant. Cell number and granulocyte – monocyte colony – forming cell (CFU-c) plating efficiency were determined before freezing and after thawing, after dilution and removal of DMSO, and after 2 to 4 hr of additional incubation. The median difference in cell number and CFU-c plating efficiency after this prolonged storage was −9 and +2%, respectively. Dilution, washing, and a 2-hr incubation were associated with cell losses of 24, 24, and 19% and increases in CFU-c plating efficiency, ranging from 22 to 79%. The number of viable CFU-c was never significantly lower than the number of CFU-c stored or initially thawed. Vapor phase storage appears to be adequate for prolonged human bone marrow cryopreservation using CFU-c viability as a determinant.

Bone marrow transplantation from HL-A matched donors to patients with acute leukemia. Toxicity and antileukemic effect.

Eleven HL-A antigen- and mixed leukocyte culture (MLC)-matched sibling bone marrow transplants were attempted in nine multiply transfused acute leukemia patients to define the toxicities of the immunosuppressive regimens and the complications associated with marrow engraftment. All patients but one were considered refractory to conventional chemotherapy. Eight of the nine patients were engrafted as indicated by a change to donor red blood cell (RBC) type, leukocyte karyotype, immunoglobulin allotype, or by the speed of marrow repopulation and/or occurrence of the graft-versus-host reaction (GVHR). The median duration of remission in the patients successfully engrafted was 67 days (range 10–132) and the median survival of all patients following preparation for marrow transplantation was 90 days (20–602). Two of four patients who developed GVHR died in remission. Four patients developed cytomegalovirus (CMV) infection during the post-transplant period.

Prolonged Granulocytopenia from Incompatible Platelet Transfusions

Abstract A prolonged decrease in circulating granulocytes accompanied transfusions of HL-A-incompatible platelet concentrates in two afebrile patients with aplastic anemia. The median granulocyte count measured at 20 hours after incompatible platelet concentrates was reduced by 30.8 per cent and remained depressed below pretransfusion levels for as long as four days (median of two days). HL-A-matched platelet concentrates obtained either from siblings or from nonfamily donors did not cause granulocytopenia. The rebound granulocytosis that usually follows transfusion reactions was not observed in these patients presumably because of severely comprised bone-marrow reserves. The prolonged delay in recovery of circulating granulocytes caused by incompatible platelet concentrates may lower host defenses and thus increase the risk of infection. (N Engl J Med 290:1220–1223, 1974)

Alteration of Sphingolipid Metabolism in Leukocytes from Patients with the Chediak–Higashi Syndrome

Abstract The synthesis and degradation of sphingolipids by mixed peripheral leukocytes from four patients with the Chediak—Higashi syndrome were studied in vitro. Incorporation of glucose uniformly...