ALBERT

Description: The effect of splenectomy on the response to random donor platelet transfusion in 15 multitransfused thrombocytopenic patients is presented. Eight patients responded poorly, with low corrected platelet count increments at 1 and 24 hours posttransfusion. These eight patients were clinically alloimmunized and had lymphocytotoxic antibody ( LCTAb ) in their sera. They responded well to closely HLA-matched transfusions. In contrast, seven splenectomized patients responded well to random donor platelets. Five of these patients had no LCTAb and no other evidence of immunization. Two patients who responded well to random donor platelets had “weak” LCTAb , and one responded to platelets presplenectomy in the presence of this antibody. Splenectomy does not improve the response to random donor platelets in alloimmunized recipients.

Description: Alloimmunization is the major complication of platelet transfusion therapy in patients with acute leukemia. To evaluate whether alloimmunization continues to be a long-term problem in patients surviving induction therapy, 114 patients with acute nonlymphocytic leukemia (ANLL) who survived more than 6 mo and who received multiple courses of chemotherapy and abundant platelet transfusions were studied. Clinical response to random donor platelets and lymphocytotoxic antibody (LCTAb) were measured pretreatment and serially throughout the study period. Fourteen patients (12%) were alloimmunized upon admission, 34 (30%) patients became alloimmunized during remission induction therapy, and 66 (58%) patients did not become alloimmunized during that period. Sixty-one of these 66 patients (92%) never became alloimmunized and responded to random donor platelets during their subsequent course despite the fact they received multiple further platelet transfusions, whereas the alloimmunized patients tended to remain alloimmunized for their entire clinical course. There was no difference in age or sex between groups, and prognostic factors predicting alloimmunization could not be detected. In greater than 90% of patients not alloimmunized at admission, the presence or absence of LCTAb after induction predicts later alloantibody production. This information can be used to plan the type of platelet transfusions (HLA-matched or random donor) needed for subsequent maintenance and induction therapy. It may also help to identify a group of patients to whom more aggressive maintenance chemotherapy may be more safely administered.

Description: In an effort to determine whether the use of leukocyte (WBC) depleted platelets could modify the development of alloimmunization, 98 adult patients with acute nonlymphocytic leukemia receiving initial induction therapy were randomized to receive standard pooled platelet concentrates (PC) or WBC-depleted PC. WBC depletion was produced by an additional centrifugation of pooled PC, with removal of 81% of WBC and an associated platelet loss of 27%. Lymphocytotoxic antibody (LCTAb) levels were monitored as a serologic marker of alloimmunization. Overall, 5 of 25 evaluable patients receiving WBC-depleted PC developed LCTAb, compared to 13/31 receiving standard PC (p = 0.071). There was no significant difference in alloimmunization rate in the subgroup of patients who had no previous exposure to histocompatibility antigens by pregnancy or prior transfusions (4/15 alloimmunized receiving WBC depleted versus 4/12 receiving standard PC). There was no difference in the number of patients in each group who required HLA-matched platelets during induction therapy. In view of the significant loss of platelets with WBC depletion, the expense and difficulty of providing WBC-poor RBC, the absence of impact on the need for HLA-matched platelets during induction, and the small potential benefit from this approach, WBC- depleted platelets should not be utilized to prevent alloimmunization in patients with leukemia.

Description: The effect of splenectomy on the response to random donor platelet transfusion in 15 multitransfused thrombocytopenic patients is presented. Eight patients responded poorly, with low corrected platelet count increments at 1 and 24 hours posttransfusion. These eight patients were clinically alloimmunized and had lymphocytotoxic antibody ( LCTAb ) in their sera. They responded well to closely HLA-matched transfusions. In contrast, seven splenectomized patients responded well to random donor platelets. Five of these patients had no LCTAb and no other evidence of immunization. Two patients who responded well to random donor platelets had “weak” LCTAb , and one responded to platelets presplenectomy in the presence of this antibody. Splenectomy does not improve the response to random donor platelets in alloimmunized recipients.

Description: In an effort to determine whether the use of leukocyte (WBC) depleted platelets could modify the development of alloimmunization, 98 adult patients with acute nonlymphocytic leukemia receiving initial induction therapy were randomized to receive standard pooled platelet concentrates (PC) or WBC-depleted PC. WBC depletion was produced by an additional centrifugation of pooled PC, with removal of 81% of WBC and an associated platelet loss of 27%. Lymphocytotoxic antibody (LCTAb) levels were monitored as a serologic marker of alloimmunization. Overall, 5 of 25 evaluable patients receiving WBC-depleted PC developed LCTAb, compared to 13/31 receiving standard PC (p = 0.071). There was no significant difference in alloimmunization rate in the subgroup of patients who had no previous exposure to histocompatibility antigens by pregnancy or prior transfusions (4/15 alloimmunized receiving WBC depleted versus 4/12 receiving standard PC). There was no difference in the number of patients in each group who required HLA-matched platelets during induction therapy. In view of the significant loss of platelets with WBC depletion, the expense and difficulty of providing WBC-poor RBC, the absence of impact on the need for HLA-matched platelets during induction, and the small potential benefit from this approach, WBC- depleted platelets should not be utilized to prevent alloimmunization in patients with leukemia.

Description: High-dose intravenous gammaglobulin (polyvalent immunoglobulin G) has been shown to be of benefit in some patients with immune thrombocytopenic purpura (ITP), possibly by producing reticuloendothelial system blockade. We studied this approach in patients refractory to random donor platelet transfusion using an IV IgG preparation manufactured by the Swiss Red Cross. Eleven adult patients with acute leukemia received either 0.4 g IgG/kg/d intravenously X five days (four patients) or 0.6 g/kg/d X five days (seven patients). All patients had high levels of lymphocytotoxic antibody and poor responses to random donor platelets. Except for mild headaches in two patients, there were no side effects related to the IgG infusions. All patients had significant elevations of serum IgG on the day after completion of treatment. Either random donor or partially HLA-matched platelet transfusions were administered the day after and, in some cases, during the IgG therapy. No patient had an improvement in one hour posttransfusion platelet count increments. Two additional patients received pooled platelet concentrates incubated for 30 minutes at 37 degrees C with IgG at a final concentration of 3 g% prior to transfusions. These results indicate that high-dose IgG, an extremely expensive treatment, cannot be recommended for alloimmunized adults with leukemia.

Description: 111In-labeled granulocytes were used to study the effects of histocompatibility factors on the migration of transfused granulocytes to infected sites. Fourteen alloimmunized and 20 nonalloimmunized patients received approximately 10(8) 111In-labeled granulocytes from ABO-compatible, non-HLA-matched donors, and scans were performed over known infected sites. All 14 alloimmunized patients had lymphocytotoxic antibody (LCTAb) and required HLA-matched platelet transfusions. Of the nonalloimmunized patients, 20/20 had positive scans at sites of infection. None of the 20 had LCTAb, 0/17 had a positive lymphocytotoxic crossmatch (LCTXM) with the donor, and 3/18 had a positive leukoagglutinin crossmatch (LAXM). Thus, histocompatibility testing was not found to be important in nonalloimmunized patients. In contrast, only 3/14 alloimmunized patients had positive scans at sites of infection (p = 0.00001 compared to nonalloimmunized patients). One of 3 had a positive LCTXM and 2/3 had a positive LAXM. Of the alloimmunized patients, 10/11 with negative scans had a positive LCTXM and 8/11 had a positive LAXM. Labeled granulocytes failed to reach sites of infection in 11/14 (78%) alloimmunized patients, demonstrating that histocompatibility factors can be of major importance in affecting the outcome of granulocyte transfusions. Granulocytes from random donors are unlikely to be effective in alloimmunized patients. The lack of an adequate crossmatching technique is a major problem limiting the ability to provide granulocyte transfusions for alloimmunized patients.

Description: Alloimmunization is the major complication of platelet transfusion therapy in patients with acute leukemia. To evaluate whether alloimmunization continues to be a long-term problem in patients surviving induction therapy, 114 patients with acute nonlymphocytic leukemia (ANLL) who survived more than 6 mo and who received multiple courses of chemotherapy and abundant platelet transfusions were studied. Clinical response to random donor platelets and lymphocytotoxic antibody (LCTAb) were measured pretreatment and serially throughout the study period. Fourteen patients (12%) were alloimmunized upon admission, 34 (30%) patients became alloimmunized during remission induction therapy, and 66 (58%) patients did not become alloimmunized during that period. Sixty-one of these 66 patients (92%) never became alloimmunized and responded to random donor platelets during their subsequent course despite the fact they received multiple further platelet transfusions, whereas the alloimmunized patients tended to remain alloimmunized for their entire clinical course. There was no difference in age or sex between groups, and prognostic factors predicting alloimmunization could not be detected. In greater than 90% of patients not alloimmunized at admission, the presence or absence of LCTAb after induction predicts later alloantibody production. This information can be used to plan the type of platelet transfusions (HLA-matched or random donor) needed for subsequent maintenance and induction therapy. It may also help to identify a group of patients to whom more aggressive maintenance chemotherapy may be more safely administered.

Description: In a case of acute promyelocytic leukemia (APL), the expression of terminal deoxynucleotidyl transferase (TdT), an early lymphoid marker, was detected. Double-fluorescent staining for the myeloid-specific antigens VIM-2 and VIM-D5 in combination with specific antiserum for TdT suggested a mixed leukemic cell population consisting of a morphologically, cytochemically, and immunologically promyelocytic component (80%) and a lymphoid, TdT+ component (20%) that was myelomonocytic in morphology but otherwise without any evidence of nonlymphoid nature. Fluorescent-activated cell analysis revealed that a greater number of cells reacted with monoclonal anti-T antibodies (OKT3, OKT6, and OKT11) than could be identified as lymphoid by TdT expression. As confirmed by double-staining fluorescence microscopy, a large fraction of the promyelocytic leukemia cells were biphenotypic, expressing both myeloid and lymphoid markers (50% positive for VIM-D5 and OKT6, 30% positive for VIM-D5 and OKT3). Subsequently, in vitro differentiation experiments were performed. While treatment of the cells with GCT-conditioned medium favored proliferation, with only a weak and delayed promotion of the cells towards maturation as reflected by enhanced expression of the mature T-marker T3 but persistent expression of the thymocyte antigen, exposure to all-trans and 13-cis retinoic acid resulted in marked differentiation of both the myeloid and the lymphoid cell characteristics. Retinoid treatment resulted in the loss of TdT, a partial disappearance of the T6-antigen, and the expression of the late T cell antigen T3 by almost 70% of the cells. In addition, myeloid maturation was obvious from the morphologic appearance of the cells, as well as from the expression of the OKM1- associated antigen by a majority of the cells. This report concerns a unique case of APL in which, for the first time, a coexistence of promyelocytic and lymphoid elements was detected, with exposure of the cultured leukemic cells to retinoic acid inducing maturation along both the myeloid and the lymphoid lineage.

Description: A major concern about the use of prophylactic platelet transfusions is the development of alloimmunization. To determine whether the rate of alloimmunization is related to the number of platelet transfusions, we measured the development of lymphocytotoxic antibody in the first 2 mo of induction therapy in patients with acute nonlymphocytic leukemia. All patients received prophylactic random donor platelets and packed red blood cells during induction. No patient had lymphocytotoxic antibody present at admission. One hundred and six patients received an average of 9.3 platelet transfusions (range 2–34) containing an average of 61 U (range 9–236). The rate of alloimmunization was 38% overall and correlated with refractoriness to platelet transfusions. Ten of 19 patients receiving less than or equal to 4 transfusions became immunized, compared with 30/87 patients receiving less than 4 transfusions. There was no relationship between the number of platelet transfusions given and the rate of severity of alloimmunization, suggesting prophylactic platelets need not be withheld expressly to prevent alloimmunization.