CLINICAL PATHOLOGIC CONFERENCE
Room M-112 DeBakey Building
Thursday, February 21, 2002
12:15-1:15 PM

Clinical Discussant: Dimitrios Kontoyiannis, M.D.
Pathologist: Suzanne Powell, M.D.
Case Preparation: Mary Ann Gaska, M.D.

Chief Complaint: The patient is a 52 year old man with a history of chronic lymphocytic leukemia who received a bone marrow transplantation on September 13, 2000. 75 days later he sustained a fall, developed altered mental status, and was found to have four ring enhancing lesions on magnetic resonance imaging.

History of Present Illness: The patient initally presented in April, 1996 with altered mental status. He was found to have a spontaneous subdural hematoma which was attributed to acquired von Willebrand factor deficiency. His peripheral smear revealed lymphocytosis and he was ultimately diagnosed with chronic lymphocytic leukemia.

Over the next three years he was treated with various regimens including steroids, cytoxan, and cyclosporine. In June, 1999, he
developed recurrent herpes zoster and was admitted for intravenous acyclovir. At the time of that admission he was noted to have
accelerating disease with increased splenomegaly, lymphadenopathy, and thrombocytopenia. He was subsequently treated with cytoxan, followed by a cycle of fludarabine in October, 1999, and in January of 2000 with CHOP.

In March, 2000, he was found to have pulmonary nodules on a chest radiograph. Sputum cultures as well as a bronchoalveolar lavage
failed to reveal any organisms. He was treated with 1300mg amphotericin B with improvement of the nodules. He was prescribed
itraconazole which he took intermittently over the next 5 months.

Because of continued pancytopenia, unresponsive to chemotherapy, he underwent a bone marrow transplantation on September 13,
2000. A "mini transplant" (submyeloablative regimen) was used because of his comorbid conditions, including the von Willebrand's disease, and the history of multiple courses of chemotherapy. Prior to the transplant he was given fludarabine, alemtuzumab (campath), and total body irradiation. On the day of transplantation, he was given levaquin, penicillin V, itraconazole, and amphotericin B.

Ceftazidime and granulocyte colony stimulating factor were added 3 days later when he became neutropenic. His course was complicated by occasional fevers for which his antibiotics were manipulated, however all cultures during this time remained negative. He was given dapsone for Pneumocystis carinii prophylaxis from October 6 to November 6.

His course was also complicated by mild graft versus host disease which manifested as a rash with grade II disease. He was treated
with steroids with improvement of the rash. Because of residual disease, the patient experienced slow engraftment of his bone marrow transplant. In order to treat the residual tumor burden, rituximab was initiated on October 7 and was given once a week for four doses.

By the middle of November, the patient admitted to feeling better with an increased appetite, and he complained only of some mild
dizziness and occasional headaches. He continued to have intermittent fevers and on November 24 ceftazidime and vancomycin were added to his medication regimen because of a temperature of 100.8°F. On November 27, the patient sustained a fall and traumatized his head. He was alert and oriented immediately after the fall, but the following day he became disoriented and confused. An emergent computed tomographic scan of the head revealed occlusion of the right lateral horn.

Magnetic resonance imaging was subsequently obtained and revealed irregularly shaped ring enhancing lesions in the left middle frontal gyrus, left parietal cortex, right parietal occipital region and right thalamus. The largest measured 3.5 centimeters in diameter and all were surrounded by vasogenic edema. None of these lesions were present on a previous computed tomagraphic scan of his head, obtained without administration of contrast, in September, 2000.

Past Medical History: Chronic lymphocytic leukemia
Peptic ulcer disease with a gastric ulcer at age 15 and duodenal ulcer at age 30
Irritable bowel syndrome
Herpes Zoster

Past Surgical History: Evacuation of subdural hematoma, April, 1996
Right inguinal hernia repair, May, 1998
Skin biopsy of the abdomen and flank in June, 1999 which revealed granuloma annulare
PICC line placement in August, 2000

Allergies: Sulfa medications, prevacid, DDAVP, heparin

Immunization status: Not recorded

Medications: Amphotericin B lipid formulation 315 mg IV QOD (changed from amphotericin B on October, 18)
Itraconazole 200 mg PO BID x 10 weeks
Levofloxacin 500 mg PO QD x 7 weeks
Penicillin V 250 mg PO Q 6 hours x 4 weeks
Vancomycin 1 g IV Q 12 hours x 4 days
Ceftazidime 1.5 g IV Q 6 hours x 4 days
Ganciclovir 300 mg IV QD Monday through Friday x 2 weeks
Tacrolimus Elixir 2 mg PO QD x 3 weeks
Methylprednisolone 32 mg PO QD (changed from IV dose, on steroids x 4 weeks)

Social History: The patient was single without any children. He denied the use of tobacco, alcohol, or any illicit substances. He previously worked in advertising over the internet. He denies any recent travel outside of Houston.

Family History: His father was diagnosed with prostate cancer at age 79 and his mother is well. Both his maternal grandmother and maternal great aunt died of gastric cancer.

Review of Systems: As above

Physical Exam (on 11/28):
In general the patient was awake but confused and had difficulty answering questions. His vital signs included a blood pressure of 117/63 mmHg with a pulse of 113 beats per minute. His respiratory rate was 20 breaths per minute and his temperature was 97° F.

HEENT: The head was normocephalic. A laceration was present on over the left temporal area with surrounding ecchymoses. The sclerae were anicteric and the conjunctivae were pale without any lesions. A fundoscopic examination did not reveal any papilledema or other retinal lesions. The oropharynx was clear and the mucousal membranes were moist. There was a hematoma on the tongue.

Neck: The neck was supple. There was no increase in jugular venous pressure, no lymphadenopathy or thyromegaly.

Cardiovascular: The heart rate and rhythm were regular without murmurs or gallops.

Chest: The lungs were clear to auscultation bilaterally.

Abdomen: The abdomen was soft, non-tender, and non-distended. Bowel sounds were present in all four quadrants. There was no
hepatosplenomegaly or masses palpated.

Rectal: The rectal tone was normal without any masses palpated. There was brown stool which was guaiac negative.

Extremities: There was no edema, cyanosis or clubbing present. Pulses were strong throughout. A PICC line was present in the left arm.

Neurologic: The patient was alert and oriented to self and to place but not to time. His cranial nerves 2-12 were intact. His strength was intact as was his sensation. Deep tendon reflexes were 1+ throughout. He did not have a Babinski reflex.

Laboratory Data: See attached laboratory flow sheet.

Electrocardiogram (11/27): Sinus tachycardia with a rate of 104. The axis and intervals were normal without any ST or T wave changes.

Chest Radiograph (11/30): The heart is enlarged and there is vascular congestion centrally, consistent with perihilar pulmonary edema.

Remainder of the Hospital Course: A neurosurgical consultation was obtained but because of the patient's severe thrombocytopenia and coagulopathy a biopsy of the lesions was not performed. Even with empiric therapy, the patient's condition rapidly declined and he expired two weeks later. An autopsy was subsequently performed.

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Contact: Donna Herrick (dherrick@bcm.tmc.edu)
URL: http://www.bcm.tmc.edu/medicine/CPC/0202_text.html
(Modified: 26-Jan-2002/km)