BRIEF REPORTGastrointestinal Relapse of Leukemia, Mimicking Acute Graft vs. Host Disease,

Following a Stem Cell Transplant

Morris Kletzel, MD,1* Dafna Meitar, MD,2 Mounif El-Youssef, MD,3 andSusan L. Cohn, MD1

Key words: acute lymphoblastic leukemia; gastrointestinal relapse; hematopoieticstem cell transplant; graft vs. host disease

Acute lymphoblastic leukemia (ALL) infiltration ofthe gastrointestinal tract is exceedingly uncommon [1,2].The few patients reported with gastrointestinal (GI) ALLhave concomitant overt bone marrow and peripheralblood involvement, although Weisdorf and colleaguesreported a patient with isolated gastroduodenal mucosalrecurrence leukemia [3]. The manifestations of GI leu-kemia are nonspecific, and many of the symptoms aresimilar to those associated with GI acute graft vs. hostdisease (GVHD) [3]. Our experience with this rare com-plication is therefore of interest. Our patient with ALLdeveloped severe abdominal pain and diarrhea resultingfrom a GI relapse following an allogeneic hematopoieticstem cell transplantation (HSCT).

The patient was a 15-year-old white female found tohave ALL in July, 1993. She presented with a WBC of290 × 109/liter, petechia, fever, and lethargy. Bone mar-row revealed an infiltrate of lymphoblasts, with FAB L1morphology. Leukemia blasts were also identified in thespinal fluid. Cell surface markers were positive forCD10, CD19, CD20, CD45, and HLA-DR. The patientwas enrolled on the high-risk Pediatric Oncology Group(POG) Protocol 9006. Induction therapy consisted of vin-cristine 1.5 mg/m2 I.V. weekly × 4, prednisone 40 mg/m2/day P.O. for 28 days, asparginase 6,000 U/m2 I.M.twice per week, doxorubicin 25 mg/m2 I.V. weekly × 4,and triple intrathecal chemotherapy. Bone marrow onday 28 revealed 22% blasts. Following 2 additionalweeks of induction chemotherapy, the patient achieved abone marrow remission, but her spinal fluid continued tobe positive for blasts. An HLA-identical sibling wasidentified, and it was elected to proceed with an alloge-neic HSCT. Prior to her transplant the patient receivedone additional cycle of consolidation chemotherapy withmitoxantrone 15 mg/m2 I.V daily × 3 days, cytarabine 1gm /m2 I.V. over 1 hr every 12 hr × 12 doses, vincristine1.5 mg/m2 I.V. weekly × 4, and prednisone 60 mg/m2/day P.O. for 28 days. Her preparation for the stem celltransplant included CNS irradiation (1,800 cGy admin-

istered in 10 180 cGy fractions) followed by TBI (12 Gyin 150 cGy fraction bid × 4 days). After the radiotherapywas completed, a continuous infusion of etoposide 1,000mg/m2/day × 2 days and cyclophosphamide 60 mg/kg/day as a 1 hrinfusion × 3 days were administered. Onday 0, the patient received 0.89 × 106 MNC/kg (0.96 ×106 CD34+ cells/kg). Engraftment was achieved by day25, and the patient was discharged from the hospital onday 28. On day 59 the patient was readmitted to thehospital with diarrhea, fever, and skin rash. A clinicaldiagnosis of GVHD was made, and this diagnosis wasconfirmed with a skin biopsy. The GVHD was not re-sponsive to increasing doses of cyclosporin A and ste-roids. However, administration of antithymocyte globu-lin and thalidomide resulted in clearing of her skin le-sions and a decrease in the diarrhea. The patient wasdischarged from the hospital in stable condition after 7days of treatment. A few days later, the patient developeda painful lumbosacral mass. The mass was excised withthe patient under general anesthesia, and pathologic ex-amination revealed recurrent leukemia. The immunophe-notype of the blasts was the same as that seen at the timeof diagnosis. No further therapy was given. One monthlater, the patient presented with fever, diarrhea, and men-tal status changes. A computed tomography (CT) scan ofthe head revealed no lesions. However, CT of the abdo-

1Department of Pediatrics, Division of Pediatric Hematology Oncol-ogy, Northwestern University Medical and School and Children’s Me-morial Hospital, Chicago, Illinois2Division of Pediatric Hematology Oncology, Tel Hashomer Hospital,Tel Aviv, Israel3Division of Pediatric Gastroenterology, Mayo Clinic School of Medi-cine, Rochester, Minnesota

*Correspondence to: Dr. Morris Kletzel, Division of Hematology/Oncology, Box 30, Children’s Memorial Hospital, 2300 Children’sPlaza, Chicago, IL 60614. E-mail: mkletzel@nwu.edu

Received 28 September 1999; Accepted 23 October 1999

Medical and Pediatric Oncology 34:287–289 (2000)

© 2000 Wiley-Liss, Inc.

Fig. 1. The duodenal biopsy reveals nearly complete effacement by the leukemia infiltrate. A portion of muscularis mucosa is visible at thebottom of the field. Hematoxilin and eosin. ×470.

Fig. 2. High power micrograph of the duodenal infiltrate reveals sheets of leukemia blasts. Hematoxilin and eosin. ×5,875.

288 Kletzel et al.

men demonstrated multiple mass lesions along her upperintestine. Endoscopy was performed, and biopsies of thestomach, duodenum, and proximal ileus were obtained,which revealed diffuse infiltration with leukemic blasts(Figs. 1, 2). Immunophenotyping studies again demon-strated the same B-precursor cell surface markers thatwere detected in her original leukemia. No evidence ofleukemia was detected in the bone marrow or CSF at thistime. No further antileukemia therapy was given, and thepatient died a few days later from multiorgan systemfailure and progressive leukemia.

DISCUSSION

The symptoms of abdominal pain and diarrhea in ourpatient clinically mimicked recurrent GVHD. However,the diagnosis of relapsed ALL was confirmed by histo-logic examination and immunologic analysis of the tissueobtained by endoscopic biopsy. GVHD of the intestine ischaracterized by an infiltrate of T cells in the laminapropia that express CD2 and CD8 [4]. In addition, endo-

thelial cells that express ICAM-1 are prominent inGVHD tissue [4]. In contrast, the gastrointestinal tissuein our patient revealed an infiltration of cells that ex-pressed CD19, CD10, and HLA-DR, markers for early Bprecursor cells. Relapsed leukemia should be consideredin the differential diagnosis of ALL patients who presentwith gastrointestinal symptoms following HSCT and failto respond to conventional treatment for GVHD.

REFERENCES

1. Cornes JA, Jones TG. Leukemic lesions of the gastrointestinaltract. J Clin Pathol 1962;15:305.

2. Prolla JC, Kirsner JB, The gastrointestinal lesions and complica-tions of the leukemias. Ann Intern Med 1964;61:1084–1103.

3. Weisdorf D, Arthur D, Rank J, et al. Gastric recurrence of acutelymphoblastic leukemia mimicking graft versus host disease. Br JHematol 1989;71:559–561.

4. Roy J, Platt JL, Weisdorf DJ. The immunopathology of uppergastrointestinal acute graft versus host disease. Lymphoid cellsand endothelial adhesion molecules. Transplantation 1993;55:572–578.

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