Case 33

Published on 18/02/2015 by admin

Filed under Allergy and Immunology

Last modified 22/04/2025

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CASE 33

A 22-year-old man is admitted to the intensive care unit (ICU) in severe respiratory distress. This unfortunate fellow was diagnosed with chronic myelogenous leukemia (CML) 6 months ago. His doctors advised both him and his family that a bone marrow transplant offered the only chance of cure. Extensive searching of relatives who were prepared to donate marrow failed to find a good match. However, searching the bone marrow transplant registry revealed one donor matched for all class I and II disparities. Transplant was performed 5 months earlier, after pretreatment with cyclophosphamide. He has had three episodes of graft-versus-host disease (GvHD), all of which resolved with pulses of anti-CD3 antibodies and corticosteroids. His current medications include cyclosporine, methotrexate, and prednisone. He has had hematuria for 10 days and watery diarrhea for 5. While in the ICU his respiratory distress worsens and there is an urgent intubation to allow for adequate oxygenation. All cultures are negative. At this stage you are not sure of what might be going on but are aware of a number of possibilities.

QUESTIONS FOR GROUP DISCUSSION

RECOMMENDED APPROACH

Implications/Analysis of Laboratory Investigations

In general, CML patients have an elevated white blood cell count (see Appendix for reference value) as well as an elevated platelet count (increase of ∼ 40%), in the absence of infection or an inflammatory response.

ETIOLOGY: GRAFT VERSUS HOST DISEASE

GvHD is not uncommon after allogeneic bone marrow transplantation. This patient was closely matched for all MHC class I/II mismatches (technically easier to do for marrow transplants when time is on your side). In contrast, when a solid organ becomes available the ischemic time (for the potential graft) limits the time available to match carefully for all incompatibilities). Matching would generally be using RFLP and/or allele-specific PCR. However, note that even after careful complete matching for MHC incompatibilities, multiple minor histologic incompatibilities are likely to be present, and often immune responses to these can generate as vigorous a rejection response as that to MHC antigens.

Clinical Presentation: GvHD or Infection?

GvHD itself presents often as a multisystem disease with gastrointestinal, lung, genitourinary, and skin involvement. Treatment of GvHD would involve a pulse of increased immunosuppressive drugs. However, an alternative cause of the presenting complaints may itself be an infectious episode, secondary to the immunosuppression to which the patient has been exposed already to allow engraftment (prevent rejection) of the bone marrow graft. This immunosuppression exposes the patient to multiple opportunistic infections (somewhat analogous to HIV infection or patients treated for autoimmune disorders), among which lung pathogens (CMV, Pneumocystis) would rank high on the list (Fig. 33-1). In addition, some of the immunosuppressive drugs used (methotrexate, in particular) can often induce hepatic and/or lung toxicity on their own accord.