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Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin
List AF, Sun Z, Verma A, Bennett JM, Komrokji RS, McGraw K, Maciejewski J, Altman JK, Cheema PS, Claxton DF, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021;:Jco2001691
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Abstract
PURPOSE Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin. METHODS In a phase III, US intergroup trial, we randomly assigned patients to receive either LEN and EPO alfa or LEN alone following stratification by serum erythropoietin concentration and prior erythropoietin treatment. RESULTS A total of 195 evaluable patients were randomly assigned: 99 patients to the LEN-EPO alfa cohort and 96 to LEN alone. After four cycles of treatment, the primary end point of major erythroid response (MER) was significantly higher (28.3%) with the combination compared with LEN alone (11.5%) (P = .004). Among 136 patients who completed 16 weeks of study treatment, 38.9% and 15.6% achieved MER, respectively (P = .004). Additionally, minor erythroid response was achieved in 18.2% and 20.8% of patients, for an overall erythroid response rate of 46.5% versus 32.3%. Among LEN nonresponders, 38 crossed over to the addition of EPO alfa with 10 patients (26.3%) achieving a MER. Responses to the combined treatment were highly durable with a median MER duration of 23.8 months compared with 13 months with LEN alone. CONCLUSION LEN restores sensitivity to recombinant erythropoietin in growth factor-insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of MER compared with LEN alone (funded by the National Cancer Institute; E2905 ClinicalTrials.gov identifier: NCT02048813).
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Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients
Slichter SJ, Davis K, Enright H, Braine H, Gernsheimer T, Kao KJ, Kickler T, Lee E, McFarland J, McCullough J, et al
Blood. 2005;105((10):):4106-14.
Abstract
A variety of patient and product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets (TRAP). Responses measured were platelet increments, interval between platelet transfusions, and platelet refractoriness. Patient factors that improved platelet responses were splenectomy and increasing patient age. In contrast, at least 2 prior pregnancies, male gender, splenomegaly, bleeding, fever, infection, disseminated intravascular coagulation, increasing height and weight, lymphocytotoxic antibody positivity, an increasing number of platelet transfusions, or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses. Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets, platelets stored for 48 hours or less, and giving large doses of platelets while ultraviolet B (UV-B) or gamma irradiation decreased platelet responses. However, in alloimmunized lymphocytoxic antibody-positive patients, the immediate increment to UV-B-irradiated platelets was well maintained, whereas all other products showed substantial reductions. Refractoriness to platelet transfusions developed in 27% of the patients. Platelet refractoriness was associated with lymphocytotoxic antibody positivity, heparin administration, fever, bleeding, increasing number of platelet transfusions, increasing weight, at least 2 pregnancies, and male gender. The only factors that reduced platelet refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets.
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Incubation of platelet concentrates before transfusion does not improve posttransfusion recovery
Hussein MA, Schiffer CA, Lee EJ
Transfusion. 1990;30((8):):701-3.
Abstract
Incubation of stored platelet concentrates (PCs) at 37 degrees C for 1 hour has been reported to result in a better morphology score and improved platelet recovery. A study was conducted in adult patients with leukemia to determine whether incubation of stored PCs results in an improved platelet recovery as measured by 10-minute posttransfusion corrected count increments (CCI). Eligible patients had platelet counts of less than 30,000 per microL and were clinically stable. Patients were transfused with 6 to 10 units of PC stored for 3 days (15 studies) or 4 days (5 studies). Platelets were pooled and then split in two equal volumes so that each patient received two sequential half-transfusions, one incubated at 37 degrees C for 1 hour and the other kept at 22 degrees C for 1 hour. Patients were randomized as to which half-transfusion was received first. The mean CCI of the incubated half-transfusions was 13.6 x 10(3) when they were given first and 14.5 x 10(3) when given second; this was not significantly different from the mean CCI of the nonincubated half-transfusions: 13.8 x 10(3) when they were given first and 13.8 x 10(3) when given second. In contrast to earlier reports, it can be concluded that incubation of pooled PCs does not improve platelet recovery.
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ABO compatibility can influence the results of platelet transfusion. Results of a randomized trial
Lee EJ, Schiffer CA
Transfusion. 1989;29((5):):384-9.
Abstract
Sixty consecutive patients with untreated acute leukemia alternately received either ABO-matched or ABO-mismatched random-donor platelet transfusions prepared from pooled platelet concentrate stored for 1 to 3 days. Patients were assigned randomly to receive matched or mismatched platelets as their first transfusion, and the first four transfusions were analyzed. In 40 evaluable patients, there was no significant difference (paired t test) between the 10-minute posttransfusion corrected count increments (CCI) of the initial transfusions of matched and mismatched platelets. In contrast, the second matched transfusion was significantly better than the second mismatched transfusion. This effect of ABO compatibility was particularly pronounced in a subset of patients. Six patients in whom mismatched transfusions were consistently inferior to matched transfusions had either a significant increase in anti-A or -B isoagglutinin titers following the first transfusion or elevated titers before or at the conclusion of the study. Conversely, in five patients in whom there was no apparent effect of ABO mismatching, only one had an increase in isoagglutinin titer. Platelet survival was not altered as the ratio of 18-hour to 10-minute posttransfusion CCl was 0.6 for both matched and mismatched platelet transfusions. These data demonstrate that ABO compatibility can affect the results of random-donor platelet transfusions and that patients who experience poor increments from ABO-mismatched platelets may benefit from a trial of ABO-compatible platelets before the initiation of HLA-matched platelet transfusion.
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A randomized trial of leukocyte-depleted platelet transfusion to modify alloimmunization in patients with leukemia
Schiffer CA, Dutcher JP, Aisner J, Hogge D, Wiernik PH, Reilly JP
Blood. 1983;62((4):):815-20.
Abstract
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.
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Alloimmunization following prophylactic granulocyte transfusion
Schiffer CA, Aisner J, Daly PA, Schimpff SC, Wiernik PH
Blood. 1979;54((4):):766-74.
Abstract
Nineteen noninfected adults receiving initial induction chemotherapy for acute nonlymphocytic leukemia (ANLL) were randomized to receive either prophylactic granulocyte transfusion or platelet transfusion alone on an alternate-day schedule. An average of 11 granulocyte transfusions (range 3--19) were administered/patient with a mean dose of 11.5 X 10(9) granulocytes/transfusion. The groups were identical with respect to age, sex, number of days on study, granulocytopenic days, percent of days receiving systemic antibiotics, febrile days, complete remission rate, and incidence of minor infection. Significant transfusion reactions were much increased in the granulocyte transfusion group (7/10 versus 1/9 in controls) and were associated with the development of lymphocytotoxic antibodies (7/10 versus 4/9 controls), refractoriness to platelet transfusion, repeated fevers, and a pulmonary infiltrate in one patient. Alloimmunization to granulocytes occurred as early as the second week in some patients complicating platelet support during induction and maintenance. No severe infections occurred in the granulocyte transfusion group while three fungal infections occurred in the controls. The high rate of alloimmunization suggests that histocompatibility considerations indicate that prophylactic granulocyte transfusion should not be routine therapy and should be studied only in investigational settings.