Radiologic Evaluation of Complications following Hematopoietic

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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Radiologic Evaluation of
Complications following
Hematopoietic Stem Cell Transplantation
Zuzana Tothova, HMS III
Gillian Lieberman, MD
11/12/2007
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Overview
ƒ Our patient R.D. : presentation on day +60 s/p auto-SCT
ƒ Primer on hematopoietic stem cell transplantation (SCT)
ƒ Common pulmonary complications of SCT
ƒ Common abdominal complications of SCT
ƒ Future of post-SCT complication imaging
Zuzana Tothova, HMS III
Gillian Lieberman, MD
Our patient R.D.: 37 y.o. man with AML
s/p autologous SCT
ƒ A 37 year old man with history of AML presents with
fever on Day +60 s/p myeloablative autologous SCT
ƒ Vital signs: T=102.9; HR=100; BP=120/70; RR=16, O2 sat:95 RA
ƒ Physical Exam: HEENT: PERRLA, EOMI, OP clear, MMM
Neck: no JVD, no LAD, neg Kernig’s&Brudz.
CV: RRR, nl S1, S2, no MGR
Lungs: CTAB, no WRR
Skin: no rashes
ƒ Labs: WBC = 9.3, Neut = 80.6%, Lymph = 11.6%
ƒ Medications: Pentamidine prophylaxis, Protonix, Lantus
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Primer on Stem Cell Transplantation
ƒ (Hematopoietic) Stem Cell Transplantation (SCT)
Bone marrow transplantation OR peripheral blood SCT.
(BMT)
(PBSCT)
ƒ Treatment of hematologic malignancies (attempt to achieve
cure by eliminating malignant cells) and solid malignancies
(as an adjunct treatment to allow more aggressive treatment)
ƒ Complications occur due to immune system dysfunction,
can be lethal
Radiologic evaluation = cornerstone for timely diagnosis of
complications
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Outline of PBSCT:
Shlomchik et al,
Nat Rev Imm 2007
Critical to know
1. donor type
2. timing after SCT
3. extent of myeloablation
& current immune status
Zuzana Tothova, HMS III
Gillian Lieberman, MD
Clinical factors to aid radiologic diagnosis:
ƒ What type of SCT did the patient receive?
• Autologous (donor = self)
• Syngeneic (donor = identical twin)
• Allogeneic (donor = HLA-matched sibling or unrelated)
ƒ How long has it been since patient’s SCT?
• 0-30 days: pre-engraftment phase
• 30-100 days: early post-transplantation phase
• 100 days+ : late post-transplantation phase
ƒ What conditioning regimen did the patient receive?
• Full myeloablation: most autologous and allogeneic SCT
• Non-myeloablative “mini-transplants”: allogeneic
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
SCT type and timing affect
nature of post-SCT complications
Type
Early
complications
(infectious, graft
failure, VOD)
Autologous/Syng
Allogeneic
Myeloablative
Non-myeloablative
Time (days)
0
Acute
GVHD
(acute,
chronic)
+
+
+
-
+
+
+
30
100
Chronic
complications
(infectious,auto
immune )
+
+
+
>100
Zuzana Tothova, HMS III
Gillian Lieberman, MD
Let’s go back to our patient now…
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Our patient R.D. with fever: Chest radiograph
1, ill-defined
opacities
2, cardiomegaly
3, ground glass
opacity/interstitial
edema
Pertinent negatives:
NO apparent pleural
effusion*
NO pneumothorax
* Costophrenic angles not
visualized, can’t tell definitively
PA Plain chest radiograph (PACS, BIDMC)
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Our patient R.D. with fever: CT of chest
Ground glass
opacities
Pericardial effusion
associated with
interstitial edema
hemorrhage
“Halo sign”
ill-defined airspace
opacities
associated with
pulm hemorrhage
associated with:
blood – pulmonary
hemorrhage
pus – pneumonia
fluid – pulmonary
edema
nodule - tumor
Pleural effusion
CT chest with contrast (PACS, BIDMC)
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Brief differential diagnosis
ƒ Immunocompetent:
(very broad)
• Tumor
• bronchoalveolar Ca
• metastases - melanoma
• Infection (pneumonia)
• organizing pneumonia
ƒ Immunocompromised:
• Infection
• Infection
• Infection
• eosinophilic pneumonia
• atypical pneumonia
• Inflammation (vasculitis)
• Wegener’s
Rx: Voriconazole for presumed Aspergillus pneumonia
CMV
PCP
Aspergillus
TB
any infection
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Other presentations of Aspergillus in SCT patients:
ƒ 2 forms of Aspergillosis
• Angioinvasive
ƒ Not to be confused with
Aspergilloma!
• Tracheobronchial
CT chest w/o contrast
Companion patient #1 (PACS, BIDMC)
CT chest w/ (top) and w/o (bottom) contrast
Coy et al, Radiographics 2005
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Companion patient #2:diffuse aspergillosis on CT
• 29 yo woman with fever and neutropenia on Day +14 s/p
induction therapy for AML
“Tree-in-Bud”
pattern
CT chest with contrast
associated with
Rossi et al.
RadioGraphics 2005
Aspergillosis
TB
M. Avium
CMV
RSV
CT chest with contrast (CAS, MGH)
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Other pulmonary complications of SCT
ƒ Pulmonary complications occur in 40-60% SCT recipients
ƒ CMV pneumonia
CT chest with contrast
ƒ Diffuse Alveolar Hemorrhage
CT chest with contrast
Coy et al, Radiographics 2005
ƒ pulmonary edema; PCP, VZV and Zygomyces pneumonia, etc.
Zuzana Tothova, HMS III
Gillian Lieberman, MD
Following the clinical course of our
patient R.D., he presents to ED 4 months
s/p auto-SCT with back pain…
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
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4 months later, our patient R.D. fails auto-SCT
ƒ 4 months s/p auto-SCT, patient presents with back pain
ƒ recurrence of disease: WBC= 54K, 94% blasts, BM biopsy
shows 90% intertrabecular space by blasts
ƒ Reinduction therapy, complicated by repeat bouts of invasive
aspergillosis
→ Unmatched, unrelated mini-allogeneic SCT (our patient
does not have a matched related or unrelated donor)
Zuzana Tothova, HMS III
Gillian Lieberman, MD
Our patient R.D. presents on day +24 s/p
allo-SCT with first complication
ƒ Day +24 s/p unmatched unrelated mini-allo SCT
ƒ patient develops fever, 3 days of worsening watery nonbloody diarrhea, diffuse abdominal pain, NB/NB vomitting,
decreased po intake secondary to nausea
ƒ WBC = 7.4, Neut = 82%, Lymph = 2%
ƒ Supine plain abdominal film demonstrating no evidence of
pneumoperitoneum or obstruction
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Our patient R.D.: diffuse bowel changes on CT
Featureless
(loss of mucosal
folds)
Diffuse
thickening
of small and
large bowel
wall (4-5 mm)
Contrast study of GI
Companion patient #3
Courtesy of Dr. Kruskal
(BIDMC)
CT abdomen and pelvis with contrast (PACS, BIDMC)
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Our patient R.D.: diffuse bowel changes on CT
Pertinent
negatives:
Halo of
hypoattenuation
within walls
a.k.a. Target sign
No obstruction
No perienteric/
pericolic fluid
No pneumatosis
associated with
Shock bowel
Inflammation
Vasculitis
CT abdomen with contrast (PACS, BIDMC)
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Brief differential diagnosis
ƒ Immunocompetent:
(very broad)
• Tumor (lymphoma)
• Infection (enteritis)
• Inflammation (Crohn’s)
• Ischemia/vasculitis
Rx: Steroids for Acute GVHD
ƒ Immunocompromised
s/p allogeneic SCT:
GVHD
GVHD
GVHD
Typhlitis
Aspergillus, Candida
Pseudomem. colitis
Zuzana Tothova, HMS III
Gillian Lieberman, MD
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Primer on Graft versus Host Disease
ƒ GVHD: occurs in patients s/p allogeneic-SCT or
immunodeficient patients receiving blood transfusions
ƒ Mechanism: donor-derived T cells attack recipient’s tissues,
severity related to degree of HLA mismatch
ƒ Sites: 95% skin, 75% liver, 50% gut
ƒ Two stages: acute (0-100 days) and chronic (100 days+)
• Acute: small and large bowel mucosa diffusely abnormal
• Chronic: esophageal strictures and webs
ƒ Prognosis dependent on early treatment – early diagnosis is
essential!
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Menu of tests: additional imaging of GVHD
ƒ U/S Doppler:
ƒ Wireless capsule endoscopy:
ƒ PET:
F-FDG PET
Dietrich et al, European Journal of Radiology 2007
Neumann et al, Gastrointestinal Endoscopy 2007
Ausberger et al, Transplantation 2007
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Other SCT-related abdominal complications
ƒ Infections (eg C.difficile → pseudomembranous colitis;
Candida, Aspergillus → microabscesses in liver, spleen, kidney)
ƒ Typhlitis (neutropenic colitis)
CT of abdomen with contrast
CT of abdomen with contrast
ƒ Hepatic veno-occlusive disease ƒ Benign Pneumatosis intestinalis
(VOD)
Coy et al, Radiographics 2005
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Summary of BMT-related complications
Pulmonary edema
DAH
CMV pneumonia
Viral (non-CMV) & bacterial
Idiopathic pulmonary
pneumonia
syndrome
Cryptogenic organizing pneumonia
Constrictive bronchial obliterans
Pulmonary proteinosis
Aspergillus
Pre-engaftment
(0-30 days)
Early
Late
post-transplantation Post-transplantation
(30-100 days)
(100 days + )
C. Difficile colitis
Hepatic VOD
Hemorrhagic cystitis (early)
Acute GVHD
Hemorrhagic cystitis (late)
Adapted from Coy et al. RadioGraphics 2005
Chronic GVHD
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
Acknowledgments:
ƒ Gillian Lieberman, MD
ƒ Maria Levantakis
ƒ Senthil Palaniappun, MD
ƒ Andrew Hines-Peralta, MD
ƒ Suzana Zorca
ƒ Paul Dieffenbach
ƒ Larry Barbaras, Webmaster
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Zuzana Tothova, HMS III
Gillian Lieberman, MD
References
ƒ Auberger J, Kendler D, Virgolini I, et al. Fluorine-18-fluorodeoxyglucose positron
emission tomography as a novel noninvasive diagnostic tool for gastrointestinal
graft-versus-host disease. Transplantation 2007; 84: 440-1
ƒ Coy DL, Ormazabal A, Godwin JD, Lalani T. Imaging Evaluation of Pulmonary
and Abdominal Complications Following Hematopoietic Stem Cell
Transplantation. RadioGraphics 2005; 25: 305-18
ƒ Dietrich CF, Jedrzejczyk M, Ignee A. Sonographic assessment of splanchnic
arteries and the bowell wall. European Journal of Radiology 2007; 64: 202-12
ƒ Neumann S, Schoppmeyer K, Lange T, et al. Wireless capsule endoscopy for
diagnosis of acute intestinal graft-versus-host disease.Gastrointestinal
Endoscopy 2007; 65: 403-9
ƒ Rossi SE, Franquet T, Volpacchio M, et al. Tree-in-Bud Pattern at Thin-Section
CT of the Lungs: Radiologic- Pathologic Overview. RadioGraphics 2005;
25: 789-801
ƒ Shlomchik WD. Graft-versus-host disease. Nature Reviews Immunology 2007;
7:340-52
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