Letter to the Edilor
INTUSSUSCEPTION IN ACUTE CHILDHOOD LYMPHOBLASTIC LEUKEMIA An Unusual Complication
Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chulalongkorn University on 01/04/15 For personal use only.
P. Micallef-Eynaud, MRCP, and 0. B. Eden, FRCP
Royal Hospital for Sick Children, Sciennes Road, Edinburgh EH9 1 LF, Scotland, United Kingdom 0
We wish to bring to the attention of readers the risk of intussusception during induction therapy for acute lymphoblastic leukemia. A 7-year-old Caucasian girl in our unit was originally admitted with a 2 week history of general malaise, lethargy, and several fainting attacks on exertion. Two days prior to admission she developed a widespread petechial rash. Her presenting hemoglobin was 4.1 g/dL, white cell count 77.6 X 109/1,and platelet count 20 X 109/L. Bone marrow studies confirmed her to have acute lymphoblastic leukemia of common type and she was entered into the Medical Research Council UKALL X Trial. She received both packed red cell and platelet transfusions prior to the start of treatment. After the patient had started steroids and received her first dose of vincristine and daunomycin, she became febrile on the second day of her induction therapy. Following a full infection screen, we began intravenous broad spectrum antibiotics (azlocillin 75 mg/kg/dose q 8 hourly and netilmicin 2.5 mg/kg/ dose q 8 hourly). The fever settled by Day 4, and with all cultures being negative, antibiotics were discontinued on Day 6. Following her second vincristine injection on Day 8 she complained of periumbilical pain. Abdominal ultrasound scan and serum amylase were both normal and the pain settled without specific therapy. However, 3 days later (Day l l ) , she once again complained of periumbilical pain, but her abdomen remained soft, nontender, and not distended. Her bowel sounds were infrequent but normal in character and we ascribed her symptoms to vincristine-induced constipation. O n Day 13 her abdominal pain worsened and became colicky in nature. She developed an intermittent fever and passed a loose stool that was positive on testing for blood. Her abdomen at this stage had become somewhat distended, not tender to palpation, and she did have infrequent high-pitched bowel Pediatric Hematolou and Oncolou, 7:389-3Y1 1990 Copyriphl 0 I990 by Hemisphere Publishiny Corporation I
389
Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chulalongkorn University on 01/04/15 For personal use only.
390
P. MICALLEF-EYNAUD A N D 0. B. EDEN
sounds. Plain abdominal radiographs showed dilated loops of small bowel. Because of fever she was recultured and once again started on intravenous azlocillin and metilmicin. By Day 15, the bouts of abdominal pain worsened, her diarrhea was more copious, and fecal occult was blood positive. She also passed slough per rectum. She continued to have intermittent fever but blood cultures were once again negative. Her abdomen showed progressive distension and repeat plain abdominal radiographs now showed a soft tissue density in the right lower quadrant in addition to the dilated bowel loops. A water-soluble contrast enema showed this to be an intussusception (caeco-colic) that could not be reduced by the procedure. Surgical reduction without the need for resection was performed. The postoperative course was one of gradual improvement, but on Day 17 she became pyrexial with rigors and lability of her hemodynamic status. Metronidazole was added to her antibiotic regime, and she required resuscitation with whole blood, fresh frozen plasma, cryoprecipitate, and platelets, and subsequently a low dose dopamine infusion to maintain renal perfusion. Blood cultures grew Klebsiellu oxytocu and the azlocillin was changed to ceftazidime following sensitivity results. She survived this septicemic episode and achieved complete hematological and clinical remission by Day 28. During the early intensification module of therapy, she did not receive vincristine and this drug was only subsequently reintroduced at 50% dosage. To date she remains in complete remission and is clinically well with a normal bowel habit. We believe that the sequence of events in our patient were due to vincristine-induced bowel dysfunction with an associated typhlitis causing an intussusception. Typhlitis or neutropenic enterocolitis often presents insidiously with waxing and waning of abdominal symptoms and signs and then may dramatically lead to a shocked, severely toxic patient within hours' requiring intensive resuscitation with broad spectrum antibiotics, blood products, and inotropic agents. Ultrasonography has been shown to be a rapid, safe, and noninvasive investigation in the diagnosis of neutropenic enterocolitis and can often be done at the patient's bedside. ' There are many reports in the literature of enterocolitis in acute leukemia, but intussusception has rarely been reported.' Out of 800 patients entered in the previous Medical Research Council study, UKALL VIII, there was a reported 2 % incidence of gut toxicity presumed to be secondary to vincristine necessitating interruption of therapy, but there were no reports of intussusception (Eden, OB. August 1989. Personal communication.) Although we diagnosed vincristine-induced dysfunction and typhlitis, we were slow to recognize the intussusception. In spite of the delay it was possible to reduce it surgically without need for resection. We conclude that intussusception during treatment of acute childhood leukemia is a rare event, but a potentially fatal one. During periods of neutrope-
LETTER TO THE EDITOR INTUSSUSCEPTION IN ALL
391
nia, any child who presents with abdominal symptoms, with or without fever, should be investigated with ultrasonography and possibly water-soluble contrast enema, especially if there is any suggestion of a mass lesion on plain radiographs.
REFERENCES Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chulalongkorn University on 01/04/15 For personal use only.
1. Gootenberg JE, et al.: Rapid diagnosis of neutropenic enterocolitis (typhlitis) by ultrasonography. Am
J Paediatr Haematol Oncol 9:222-227, 1987. 2. Dudgeon DL, et al.: Intussusception complicating the treatment of malignancy in childhood. Arch Surg 105(1):52-56, 1972. 3. Eden OB: Coordinator Medical Research Council, UKALL VIII toxicity (personal communication).
Received Novembn 9, 1989 Accepted March 1, I990
INTUSSUSCEPTION IN ACUTE CHILDHOOD LYMPHOBLASTIC LEUKEMIA An Unusual Complication
Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chulalongkorn University on 01/04/15 For personal use only.
P. Micallef-Eynaud, MRCP, and 0. B. Eden, FRCP
Royal Hospital for Sick Children, Sciennes Road, Edinburgh EH9 1 LF, Scotland, United Kingdom 0
We wish to bring to the attention of readers the risk of intussusception during induction therapy for acute lymphoblastic leukemia. A 7-year-old Caucasian girl in our unit was originally admitted with a 2 week history of general malaise, lethargy, and several fainting attacks on exertion. Two days prior to admission she developed a widespread petechial rash. Her presenting hemoglobin was 4.1 g/dL, white cell count 77.6 X 109/1,and platelet count 20 X 109/L. Bone marrow studies confirmed her to have acute lymphoblastic leukemia of common type and she was entered into the Medical Research Council UKALL X Trial. She received both packed red cell and platelet transfusions prior to the start of treatment. After the patient had started steroids and received her first dose of vincristine and daunomycin, she became febrile on the second day of her induction therapy. Following a full infection screen, we began intravenous broad spectrum antibiotics (azlocillin 75 mg/kg/dose q 8 hourly and netilmicin 2.5 mg/kg/ dose q 8 hourly). The fever settled by Day 4, and with all cultures being negative, antibiotics were discontinued on Day 6. Following her second vincristine injection on Day 8 she complained of periumbilical pain. Abdominal ultrasound scan and serum amylase were both normal and the pain settled without specific therapy. However, 3 days later (Day l l ) , she once again complained of periumbilical pain, but her abdomen remained soft, nontender, and not distended. Her bowel sounds were infrequent but normal in character and we ascribed her symptoms to vincristine-induced constipation. O n Day 13 her abdominal pain worsened and became colicky in nature. She developed an intermittent fever and passed a loose stool that was positive on testing for blood. Her abdomen at this stage had become somewhat distended, not tender to palpation, and she did have infrequent high-pitched bowel Pediatric Hematolou and Oncolou, 7:389-3Y1 1990 Copyriphl 0 I990 by Hemisphere Publishiny Corporation I
389
Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chulalongkorn University on 01/04/15 For personal use only.
390
P. MICALLEF-EYNAUD A N D 0. B. EDEN
sounds. Plain abdominal radiographs showed dilated loops of small bowel. Because of fever she was recultured and once again started on intravenous azlocillin and metilmicin. By Day 15, the bouts of abdominal pain worsened, her diarrhea was more copious, and fecal occult was blood positive. She also passed slough per rectum. She continued to have intermittent fever but blood cultures were once again negative. Her abdomen showed progressive distension and repeat plain abdominal radiographs now showed a soft tissue density in the right lower quadrant in addition to the dilated bowel loops. A water-soluble contrast enema showed this to be an intussusception (caeco-colic) that could not be reduced by the procedure. Surgical reduction without the need for resection was performed. The postoperative course was one of gradual improvement, but on Day 17 she became pyrexial with rigors and lability of her hemodynamic status. Metronidazole was added to her antibiotic regime, and she required resuscitation with whole blood, fresh frozen plasma, cryoprecipitate, and platelets, and subsequently a low dose dopamine infusion to maintain renal perfusion. Blood cultures grew Klebsiellu oxytocu and the azlocillin was changed to ceftazidime following sensitivity results. She survived this septicemic episode and achieved complete hematological and clinical remission by Day 28. During the early intensification module of therapy, she did not receive vincristine and this drug was only subsequently reintroduced at 50% dosage. To date she remains in complete remission and is clinically well with a normal bowel habit. We believe that the sequence of events in our patient were due to vincristine-induced bowel dysfunction with an associated typhlitis causing an intussusception. Typhlitis or neutropenic enterocolitis often presents insidiously with waxing and waning of abdominal symptoms and signs and then may dramatically lead to a shocked, severely toxic patient within hours' requiring intensive resuscitation with broad spectrum antibiotics, blood products, and inotropic agents. Ultrasonography has been shown to be a rapid, safe, and noninvasive investigation in the diagnosis of neutropenic enterocolitis and can often be done at the patient's bedside. ' There are many reports in the literature of enterocolitis in acute leukemia, but intussusception has rarely been reported.' Out of 800 patients entered in the previous Medical Research Council study, UKALL VIII, there was a reported 2 % incidence of gut toxicity presumed to be secondary to vincristine necessitating interruption of therapy, but there were no reports of intussusception (Eden, OB. August 1989. Personal communication.) Although we diagnosed vincristine-induced dysfunction and typhlitis, we were slow to recognize the intussusception. In spite of the delay it was possible to reduce it surgically without need for resection. We conclude that intussusception during treatment of acute childhood leukemia is a rare event, but a potentially fatal one. During periods of neutrope-
LETTER TO THE EDITOR INTUSSUSCEPTION IN ALL
391
nia, any child who presents with abdominal symptoms, with or without fever, should be investigated with ultrasonography and possibly water-soluble contrast enema, especially if there is any suggestion of a mass lesion on plain radiographs.
REFERENCES Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chulalongkorn University on 01/04/15 For personal use only.
1. Gootenberg JE, et al.: Rapid diagnosis of neutropenic enterocolitis (typhlitis) by ultrasonography. Am
J Paediatr Haematol Oncol 9:222-227, 1987. 2. Dudgeon DL, et al.: Intussusception complicating the treatment of malignancy in childhood. Arch Surg 105(1):52-56, 1972. 3. Eden OB: Coordinator Medical Research Council, UKALL VIII toxicity (personal communication).
Received Novembn 9, 1989 Accepted March 1, I990
