A medical consultant for a transfusion laboratory serving an oncology institute in Canada reports that a discussion is currently taking place among the physicians regarding the need (or lack of need) for irradiation of red cells (and other cellular blood products) destined for transfusion to patients with low-grade, non-Hodgkin's Lymphoma treated with Fludarabine and/or similar drugs. Currently the inquiring physician’s institution irradiates cellular blood products upon request. However they find that for the same patient, irradiated products may be ordered by the treating physician on one day, and "not required" by a different oncologist a few days later. Informal discussions with colleagues and a literature review reveal that both the published literature and local practice is quite variable in its recommendations. The inquiring physician’s oncology colleagues point out that many large treatment trials in this patient group have not required the use of irradiated blood products. On the other hand, the inquiring physician’s impression from speaking with transfusion medicine colleagues is that irradiation for this patient group is fairly common and has little "downside" if performed immediately before transfusion. The inquiring physician is interested in learning how other institutions and colleagues approach the use of irradiated blood products for this patient group.

The following responses were received.

ADDENDA Nov. 10, 2003

1. A colleague in Alaska reports that in her opinion, given the likelihood that a patient with transfusion-associated graft-versus-host disease would die, it is appropriate to irradiate cellular blood products intended for transfusion of such patients. She adds that at the recent AABB meeting in San Diego, CA, George Garratty stated that his laboratory is seeing drug-induced auto-immune hemolytic anemia associated with Fludarabine with increased frequency. That only further solidified the Alaskan's mind that irradiation of cellular blood components is appropriate and indicated for such patients. She believes that this drug is affecting the immune system in an unusual way and until that mechanism is elucidated it would seem that irradiation of cellular components is a prudent step.

ADDENDA Nov. 14, 2003

2. A colleague at the Mayo Clinic reports they agree with the correspondent from Alaska and routinely irradiate cellular blood products for such patients.

ADDENDA Nov. 24, 2003

3. A physician at the Banco de Sangre de Cantabria in Spain believes that the data support irradiation of cellular blood products for patients on fludarabine as sound policy:

• Patients with B-cell non-Hodgkin´s lymphoma are at higher risk of GVHD. The SHOT group reported this (5 of 12 GVHD reported were B-NHL) and recommended irradiation for B-NHL.
• Patients with B-cell lymphoma are frequently treated with fludarabine, which produces a profound immunosuppression.
  

Thus, products for these patients should be routinely irradiated. At the responding colleague's university hospital all lymphoma patients receive irradiated, leukocyte-reduced red cells and platelets.

ADDENDA Nov. 26, 2003

4. A transfusion medicine colleague in Sacramento would strongly support the use of irradiated cellular blood products after the administration of fludarabine. Unfortunately, her facility is aware of a case of TA-GVHD in their geographic area. This case was published in Transfusion (Hutchinson K, Kopko PM, Muto KN et al. Early diagnosis and successful treatment of a patient with transfusion-associated GVHD with autologous peripheral blood progenitor cell transplantation Transfusion 2002;42:1567-1572.) Briefly, the patient received four monthly cycles of fludarabine for treatment of CLL. The fludarabine was followed by 4 cycles of CHOP as well as radioimmunotherapy. Nine days after the radioimmunotherapy the patient received an autologous progenitor cell infusion as an outpatient. Two days after the PBSC infusion the patient was admitted to another hospital where she received 2 unit of non-irradiated packed RBCs and 3 units of non-irradiated plateletpheresis. Nine days after the transfusion the patient presented with early TA-GVHD. HLA typing by DNA methods showed a chimeric phenotype. Based upon the new antigens present in the patient's HLA type, the authors were able to implicate one of the units of RBCs as the cause of the TA-GVHD. According to the reporting physician, the fortunate part of the story is that there were sufficient PBSCs in the freezer for another transplant, to rescue the patient from GVHD. The patient received a preparative regimen similar to what a patient with aplastic anemia would receive and then she received the autologous PBSCs. Not only did the patient recover from the TA-GVHD, her CLL went into remission. The reporting physician comments that after she relived this story she feels like adding a disclaimer - "Don't try this at home". After having done this once, she would just as soon never experience this again. Additionally, most patients do not have autologous PBSCs stored for future use. Therefore, the reporting physician's institution strongly encourages irradiation of all cellular blood products for patients who have received fludarabine or 2-CDA.

ADDENDA Dec. 12, 2003

5. The Editor refers colleagues to an article cited in Doctor's Guide, about a recent report of TA-GVHD in a patient with lupus nephritis treated with fludarabine. Reference: Leitman SF et al. Transfusion Dec. 2003. The authors state: 'Irradiation of blood components should be considered in all patients who receive fludarabine therapy.'

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator