Letters to the Editor 4. Tucker J, Murphy MF, Gregory WM, et al. Apparent removal of graft-versus-leukemia effect by use of leucocyte-poor blood components in patients with acute myeloblastic leukaemia (letter). Br J Haematol 1989;73:572-4. 5. Spellman CW,Daynes RA. Modification of immunological potential by ultraviolet radiation. 11. Generation of suppressor cells in short-term W-irradiated mice. Transplantation 1977;24:120-6.

White cell reduction, ultraviolet irradiation, and platelet refractoriness in acute myeloid leukemia To the Editor: In their editorial’ in the September 1991 issue of TRANSFUSION, Nemo and McCurdy described the Trial to Reduce Alloimmunization to Platelets (TRAP). We wish to raise two questions about the study’s design and endpoints. First, will the transfused platelets be ABO-identical with the recipient? ABO mismatching may be the second most important cause of refractoriness, after sensitization to HLA-A,B. Two randomized trials recently demonstrated that the use of ABO-unmatched platelets is associated with a several-fold increase in the rate of clinical refractorines~.~*’ Second, will overall clinical outcome-that is, the remission rate and the duration of remission-be studied? Immunocompetence may play a role in remission duration in acute myeloid leukemia. There is reason to believe that white cell (WBC) reduction and ultraviolet ( W ) radiation could have either beneficial or deleterious effects on recipient immunologic function. WBC-reduced transfusions may be less immunosuppressive than standard transfusions. Conversely, the only randomized trial addressing this issue suggests that WBC reduction may abrogate a beneficial graft-versus-leukemia effect in that disease. The transfusion of W-treated WBCs may cause tolerance to HLA-A,B antigens. However, the transfusion of WBCs from W-treated animals may lead to decreased resistance to tumor cells in recipient^.^ Conversely, the transfusion of irradiated WBCs could have an adjuvant, immunostimulatory effect, perhaps analogous to that of the transfusion of W-irradiated autologous blood during photopheresis for cutaneous T-cell lymphoma. In summary, a consistent approach to ABO matching or the transfusion of ABO-unmatched platelets is necessary if the study’s outcome is not to be compromised by this confounding variable. The TRAP study additionally offers the possibility of studying the effects of blood component modification on leukemia recurrence and survival. If transfusion of W-irradiated blood reduces clinical refractoriness, it also will be essential to establish whether it has any beneficial or deleterious effect on the course of leukemia. NEIL BLUMBERG,MD Transfusion Medicine Unit University of Rochester Medical Center Bar 608, 601 Elmwood Avenue Rochester, NY 14642 JOANNA M. HEAL, MRCP Hematology Unit, Deptartment of Medicine University of Rochester Medical Center and American Red Cross Blood Services Rochester, NY 14607

The above letter was sent to Drs. Nemo and McCurdy, who offered the following reply. Thanks are due to Drs. Blumberg and Heal for their comments on our recent editorial’ and to the editors of TRANSFUSION for the opportunity to reply. Many details of the protocol for the Trial to Reduce Alloimmunization to Platelets (TRAP) were purposely omitted as more appropriate to reports of the trial’s results. Nevertheless, we are pleased to respond to the questions raised. In the TRAP study, “refractory due to alloimmunization” is defined in part by a platelet transfusion test sequence that includes fresh platelets that are ABO groupcompatible. Because selection of ABO groupcompatible platelet transfusion is logistically difficult and probably not clinically necessary, platelets for transfusion within the treatment and control arms before an inadequate platelet count response is found were not necessarily selected by ABO group. Nevertheless, the TRAP investigators discussed the data of Carr et a1.2 during protocol development, and it was recommended that all trial sites be encouraged to provide patients with ABO-compatible platelet transfusions whenever possible. It seems certain that ABO compatibility (or identity?) improves the recovery and survival of transfused platelets. Less certain, we think, is the proper place for ABO matching in platelet transfusion therapy, be it sporadic or one-time, shortterm in support of patients with leukemia undergoing induction treatment, or long-term to prevent or treat bleeding in those with aplastic anemia. Carr et aLz presented a worst-case scenario in the test arm; all platelets were ABO-mismatched and of the same incompatible group. The clinical situation is more likely to be a nonsystematic rather than a random selection of platelets, with some or all of the concentrates being of the same ABO group because of the way they are shelved. With random-number randomization, chance alone makes it likely that about one-third of the platelets in each transfusion and in each treatment course would be ABO-identical. We eagerly await the further analysis and complete description of the study by Heal et al.,3 as promised in the abstract. Although the primary purpose of the TRAP study is to determine the best way to reduce or prevent alloimmunization to platelets, the clinical status of the patients after remission induction will be also followed monthly for 1 year and every 6 months thereafter for the duration of the study. Other than HLA- and platelet-antigen specific antibodies, no studies of immunologic status are planned, but leukemia status will be determined and analyzed by treatment arm if such is deemed necessary and appropriate.

References 1. Nemo GJ, McCurdy PR. Prevention of platelet alloimmunization (editorial). Transfusion 1991;31:584-6. 2. Can R, Hutton JL, Jenkins JA, Lucas GF, Amphlett NW.Transfusion of ABO-mismatched platelets leads to early platelet refractoriness. Br J Hacmatol 1990;75:408-13. 3. Heal I, Rowe I, McMican A, Finke C, Blumberg N. A randomized trial of ABO identical versus ABO unmatched platelet transfusions (abstract). Blood 1989;74(Suppl 1):215a.

PAULR. MCCURDY,MD Bone Marrow TransplantationBranch Division of Blood Diseases & Resources National Heart, Lung, & Blood Institute Federal Building, Room 5C04 7550 Wisconsin Avenue

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‘IRANSN SION 1992-Vol. 32, No. 1

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LETTERS TO THE EDITOR

Bethesda, MD 20892 GEORGEJ. NEMO,PHD TransrfusinMedicine Branch National Heart, Lung, & Blood Institute

References Nemo GJ, McCurdy PR. Prevention of platelet alloimmunization (editorial). Transfusion 1991;31:584-6. Can R, Hutton JL, Jenkins JA, Lucas GF, Amphlett NW. Transfusion of ABO-mismatched platelets leads to early platelet refractoriness. Br J Haematol 1990,75:408-13. Heal J, Rowe J, McMican A, Finke K, Blumberg N. A randomized trial of ABO identical versus ABO unmatched platelet transfusions (abstract). Blood 1989;74(Suppl 1):215a.

Autologous blood donation in “high-risk” patients To the Editor:

The recent article by Spiess et al.’ in TRANSFUSION has contributed to our understanding of autologous blood donation by documenting physiologic changes during phlebotomy, but some unwarranted inferences may be drawn from the results. A minority of patients in the study demonstrated significant changes in systolic and diastolic blood pressure and heart rate. Are such changes clinically important? Do they presage cardiovascular decompensation or other serious sequelae, or are they simply markers of previously documented disease? Given the underlying medical problems of the study patients and the fact that there were no serious adverse reactions, could not these findings be interpreted as further evidence of the safety of autologous blood donation? We agree with the authors that studies such as theirs require an analysis of age-matched controls. Only with such controls can the frequency and significance of comparable impressive physiologic alterations be ascertained. Spiess et al.’ suggested that the use of saline infusion either following or simultaneous with phlebotomy may be important in preventing adverse outcomes related to hypotension. Are the authors implying that saline infusion should be used routinely? Might this recommendation be applied to all autologous blood donors, as undetected cardiovascular disease may be present? We have previously demonstrated, in a study involving a large and comparable patient population,2 that autologous blood donation can be accomplished with relative safety without the administration of saline. The patients in our study donated blood (for autologous use) in out-of-hospital settings. Four donations (of 886) resulted in reactions that required medical intervention, but the patients’ medical histories had failed to reveal distinguishing features from which serious reactions could have been predicted. Similarly, Spiess et al.’ were unable to predict hemodynamic changes from donor-related variables. Yet clinically significant reactions, even in donors with documented cardiovascular disease, are extremely infrequent. Restricting autologous blood donation to situations in which saline infusions (and possible monitoring) are available seems unwarranted for most donors. Although we support greater use of intraoperative cell salvage and perioperative hemodilution for Cardiovascular or other surgical procedures, such blood conservation techniques alone do not eliminate the need for allogeneic blood. Therefore, published studieszJ and extensive experience indicating the clinical safety of autologous blood donation under only moderately restrictive acceptance criteria should be relied on. Autologous blood donation should remain an important tool for transfusion

safety in patients with hemodynamically stable cardiovascular disease. At the same time, autologous blood donation should be used only when there is a reasonable likelihood of blood use. h h R K A. POPOVSKY, MD American Red Cross Blood Service Northeast Region 180 Rustcmjl Road De&m, M A 02026 and Harvard Medical School Boston, u4 02215 JAMESP. AUBUCHON,MD Dartmouth-Hitchcock Medical Center Lebanon, NH 03756

References 1. Spiess BD, Sassetti R, McCarthy RJ, Narbone RF, Tuman KJ, Ivankovich AD. Autologous blood donation: hernodynamics in a high-risk patient population. Transfusion 1992;32:17-22. 2. AuBuchon JP, Popovsky MA. The safety of preoperative autologous blood donation in the nonhospital setting. Transfusion 1991;31:513-7. 3. Owing DV, Kruskall MS, Thurer RL, Donovan LM.Autologous blood donations prior to elective cardiac surgery. Safety and effect on subsequent blood use. JAMA 1989;262:1963-8. 4. Nicholls MD, Janu MR, Davits VJ, Wedderbun CE. Autologous blood transfusion for elective surgery. Med J Aust 1986;144:3969. 5. Mann M, Sacks HJ, Goldfinger D. Safety of autologous blood donation prior to elective surgery for a variety of potentially “highrisk” patients. Transfusion 1983;23:229-32.

The above letter was sent to Dr. Spkss, who offered the following reply. I appreciate the opportunity to respond to the letter by Popovsky and AuBuchon. The questions they raise are precisely the ones that need to be answered. With respect to the blood pressure changes noted, it would have to be said that some were clinically significant. Five patients had syncope (with hypotension), seven had dysrhythmias ranging from premature ventricular contractions to new atrial fibrillation with syncope, and one patient had transient ST-T wave changes with hypotension. All were successfully treated. Clearly the majority of hypotensive changes were of no clinical significance, as one would expect. Syncope, ST-T wave changes, and cardiac rhythm changes are no doubt clinically important. The rhythm changes and the ST-T wave changes would not be discovered without monitoring. Syncope would be obvious. There were no deaths, myocardial infarction, or other “major disasters” in this group of patients. The lack of such ultimate adverse events does not negate the expressed concern that such hemodynamic changes in the face of ischemic heart disease are at the least worrisome. They may be markers of the underlying disease, and as such, they should not be ignored. The majority of literature published has stated that autologous blood donation is safe in such a high-risk population. Our study is flawed because it does not have age-matched controls. A large, prospective, age-matched controlled study with hemodynamic monitoring should be carried out. The crux of the issue being discussed is that the number of complications discovered is dependent on the sensitivity of the instruments used to find them. Our study used more sensitive instrumentation than previous studies, which relied on subjective complaints or the irrefutable endpoint, syncope. If even more sensitive

White cell reduction, ultraviolet irradiation, and platelet refractoriness in acute myeloid leukemia.

Letters to the Editor 4. Tucker J, Murphy MF, Gregory WM, et al. Apparent removal of graft-versus-leukemia effect by use of leucocyte-poor blood compo...
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