GI Case Conference

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GI Case Conference

• Irteza Inayat, MD
• 02/08/08

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History

• 38yo M s/p matched sibling donor (F?M) stem cell
  transplant for recurrent NKT-cell lymphoma
• GI team was consulted for diarrhea on day 30
  post transplant
• Onc Hx
• Presented with left testicular pain in June 2006,
  referred to urology. A left orchiectomy 07/06
  showed NKT-cell lymphoma
• Treated in 08/06 with HyperCVAD followed by
  consolidation with high-dose BEAM and autologous
  stem cell rescue
• In 05/07, he had recurrence of his disease and
  was treated with Radiation Therapy
• In 09/07, complained of decreased vision in his
  right eye? vitreal biopsy confirmed recurrent
  lymphoma
• Patient underwent a MSD SCTx in 11/07.

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• PMHx
• - DM2
• PSHx
• - none
• Allergies
• - none
• SHx
• - denies tobacco, Etoh, Illicit drug use
• FHx
• - non-contributory

• Medications
• Lantus
• Prednisone
• Tacrolimus
• MMF (cellcept)
• Protonix
• Oxycodone
• Prochlorperazine
• Ativan
• Folic Acid
• MVI
• Voriconazole
• Pentamidine

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• HPI
• Day 30 Post-Transplant
• Patient complained of loose watery stools 8-10
  BMs/d (Volume1500-1800cc per day). No blood or
  mucous in stools. Not related to eating, included
  nocturnal episodes.
• Denied any associated abdominal pain/cramping,
  nausea or vomiting. Occasional bloating was
  reported.
• No fevers, chills, rash, change in his diet
  recently, no recent travel and no prior similar
  complaints
• No personal or family history of GI disease
• No hx of jaundice or pruritus
• No recent changes in medication

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• Physical Exam
• VITALS 98.6ºF 88 127/84 98 RA
• GEN AO X 3, appears to be uncomfortable
• HEENT dry mmm, Ø LAN, Ø pallor, anicteric
• CHEST CTA b
• CV RRR Ø r/m/g
• ABD soft bs NT/ND no HSM
• EXT Ø c/c/e
• NEURO non-focal
• Rectal Normal tone, no tenderness, heme negative

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Labs
111
10.1
142
27
3.9
154
41
3.8
24.1
1.1
29.3
ANC 3.4 Diff normal
INR 1.2 ALB 3.1 LFTs WNL
Tacro 15 BCx neg Amylase/Lipase WNL
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Labs

• Stool Studies Other Serologies
• Stool Cx normal flora CMV Ag (blood) neg
• Stool WBC neg
• C Diff toxin neg
• Rectal swab neg for VRE
• Rotavirus Ag neg
• Adenovirus PCR neg
• Norovirus PCR neg

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What is the Differential Diagnosis?
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DDx

• Preconditioning regimen (mucositis)
• GVHD
• CMV infection
• Cryptosporidum
• Cyclosporin
• MMF (cellcept)
• C diff colitis
• Other viral Illnesses

What would you do next?
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• EGD
• Small hiatal hernia, otherwise normal appearing
  mucosa, biopsies done
• Colonoscopy
• Normal appearing TI and colonic mucosa, biopsies
  done
• Pathology

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• Hospital Course
• Patient was started on treatment for GVHD with
  high dose steroids, and cyclosporine and MMF were
  continued
• Repeat stool studies were negative again
• Pt continued to have 1 liter of stool output
• Repeat scope pursued on post-transplant day 41

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• EGD
• Normal appearing mucosa, biopsies were done
• Colonoscopy
• Edematous and erythematous distal TI mucosa was
  biopsied
• Mildly erythematous colonic mucosa was also
  biopsied
• Pathology
• - CMV ILEITIS WITH ULCERATION
• IMMUNOSTAIN FOR CMV IS CONFIRMATORY
• Gastric, duodenal and colonic mucosa without
  significant abnormality
• Colonic mucosa did not show the features of GVHD
  seen on previous biopsies.

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• Hospital Course
• Reactivated CMV ? Ag () and CMV cells/200,000
  ? 55
• Ganciclovir was started

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Hospital Course

• Repeat stool studies were negative again
• Patient did not report any change in his symptoms
  during this time with continued diarrhea
• CMV Ag was negative now
• GI was consulted again on post-transplant day 60

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• Further work up???

• Colonoscopy
• Mild erythema of colonic mucosa
• Edematous and narrowed IC valve, diffusely
  erythematous, friable and hemorrhagic TI mucosa
  with loss of villous pattern

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• Colonic GVHD
• Whose most at risk?
• HLA-mismatched donor
• Unrelated HLA- matched donor
• Dose of preconditioning regimen
• F donor?M recipient
• age
• CML
• In a pt with BMT, what is the most common cause
  of diarrhea?
• 100d ? Infection, Chronic GVHD, Pancreatic
  insufficiency

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In general, survival and grade of GVHD are
inversely related
How do you gauge severity of GI GVHD?
(Curr Opin in Gastroenterology 2005, 2164-69)
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• Diagnosis
• Apoptosis on a mucosal biopsy is required to make
  a diagnosis of GI GVHD
• In a series of post-HSCT patients with diarrhea,
  gastric biopsy proved to be the single most
  useful test in establishing a diagnosis of acute
  GVHD in 22 of 26 patients (Gastroenterology 1994,
  1071398-1407)
• Some studies have shown that small bowel biopsies
  are more fruitful than gastric samples
  (Endoscopy, 1996, 28680-685, Blood 2002,
  993033-3040)
• Endoscopically normal examinations are reported
  in 18 of GI GVHD patients (Transplantation 1991,
  51642-646)
• Current recommendation is to biopsy stomach,
  duodenum and rectum routinely when patients are
  referred for evaluation of potential acute GVHD
  (Curr Opin in Gastroenterology 2005, 2164-69)

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• CMV enterocolitis
• Reactivation of CMV following HSCT occurs in
  60-80 of patients
• CMV enterocolitis is the 2nd most common
  end-organ manifestation
• Incidence of CMV enteritis at 2 years post-Tx
  averaged 2
• Median time to diagnosis was 91 days post-Tx
  (range, 17-527 days)
• Viremia detected in two thirds of patients with
  CMV prior to detection of enteritis
• Overall survival was 35 at 2 years following the
  onset of eneteritis
• (Biology of Blood and Marrow Transp 2001,
  7674-679)

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• Patient follow up
• On day 70, diarrhea started to improve with
  decrease in stool frequency and volume
• Pt was discharged home on ganciclovir, steroid
  taper, cellcept and tacrolimus
• Diarrhea continues to improve with 2-3 loose
  BMs/day (Volume 300-400cc per day)