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1 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 2 Zuzana Tothova, HMS III Gillian Lieberman, MD Overview Our patient R.D. : presentation on day +60 s/p auto-SCT Primer on hematopoietic stem cell transplantation (SCT) Common pulmonary complications of SCT Common abdominal complications of SCT 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 A 37 year old man with history of AML presents with fever on Day +60 s/p myeloablative autologous SCT Vital signs: T=102.9; HR=100; BP=120/70; RR=16, O2 sat:95 RA 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 Labs: WBC = 9.3, Neut = 80.6%, Lymph = 11.6% Medications: Pentamidine prophylaxis, Protonix, Lantus 3 Zuzana Tothova, HMS III Gillian Lieberman, MD Primer on Stem Cell Transplantation (Hematopoietic) Stem Cell Transplantation (SCT) Bone marrow transplantation OR peripheral blood SCT. (BMT) (PBSCT) Treatment of hematologic malignancies (attempt to achieve cure by eliminating malignant cells) and solid malignancies (as an adjunct treatment to allow more aggressive treatment) Complications occur due to immune system dysfunction, can be lethal Radiologic evaluation = cornerstone for timely diagnosis of complications 4 5 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: What type of SCT did the patient receive? • Autologous (donor = self) • Syngeneic (donor = identical twin) • Allogeneic (donor = HLA-matched sibling or unrelated) 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 What conditioning regimen did the patient receive? • Full myeloablation: most autologous and allogeneic SCT • Non-myeloablative “mini-transplants”: allogeneic 6 7 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… 8 9 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) 10 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) 11 Zuzana Tothova, HMS III Gillian Lieberman, MD Brief differential diagnosis Immunocompetent: (very broad) • Tumor • bronchoalveolar Ca • metastases - melanoma • Infection (pneumonia) • organizing pneumonia Immunocompromised: • Infection • Infection • Infection • eosinophilic pneumonia • atypical pneumonia • Inflammation (vasculitis) • Wegener’s Rx: Voriconazole for presumed Aspergillus pneumonia CMV PCP Aspergillus TB any infection 12 Zuzana Tothova, HMS III Gillian Lieberman, MD Other presentations of Aspergillus in SCT patients: 2 forms of Aspergillosis • Angioinvasive 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 13 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) 14 Zuzana Tothova, HMS III Gillian Lieberman, MD Other pulmonary complications of SCT Pulmonary complications occur in 40-60% SCT recipients CMV pneumonia CT chest with contrast Diffuse Alveolar Hemorrhage CT chest with contrast Coy et al, Radiographics 2005 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… 15 Zuzana Tothova, HMS III Gillian Lieberman, MD 16 4 months later, our patient R.D. fails auto-SCT 4 months s/p auto-SCT, patient presents with back pain recurrence of disease: WBC= 54K, 94% blasts, BM biopsy shows 90% intertrabecular space by blasts 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 Day +24 s/p unmatched unrelated mini-allo SCT patient develops fever, 3 days of worsening watery nonbloody diarrhea, diffuse abdominal pain, NB/NB vomitting, decreased po intake secondary to nausea WBC = 7.4, Neut = 82%, Lymph = 2% Supine plain abdominal film demonstrating no evidence of pneumoperitoneum or obstruction 17 18 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) 19 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) 20 Zuzana Tothova, HMS III Gillian Lieberman, MD Brief differential diagnosis Immunocompetent: (very broad) • Tumor (lymphoma) • Infection (enteritis) • Inflammation (Crohn’s) • Ischemia/vasculitis Rx: Steroids for Acute GVHD Immunocompromised s/p allogeneic SCT: GVHD GVHD GVHD Typhlitis Aspergillus, Candida Pseudomem. colitis Zuzana Tothova, HMS III Gillian Lieberman, MD 21 Primer on Graft versus Host Disease GVHD: occurs in patients s/p allogeneic-SCT or immunodeficient patients receiving blood transfusions Mechanism: donor-derived T cells attack recipient’s tissues, severity related to degree of HLA mismatch Sites: 95% skin, 75% liver, 50% gut Two stages: acute (0-100 days) and chronic (100 days+) • Acute: small and large bowel mucosa diffusely abnormal • Chronic: esophageal strictures and webs Prognosis dependent on early treatment – early diagnosis is essential! 22 Zuzana Tothova, HMS III Gillian Lieberman, MD Menu of tests: additional imaging of GVHD U/S Doppler: Wireless capsule endoscopy: PET: F-FDG PET Dietrich et al, European Journal of Radiology 2007 Neumann et al, Gastrointestinal Endoscopy 2007 Ausberger et al, Transplantation 2007 23 Zuzana Tothova, HMS III Gillian Lieberman, MD Other SCT-related abdominal complications Infections (eg C.difficile → pseudomembranous colitis; Candida, Aspergillus → microabscesses in liver, spleen, kidney) Typhlitis (neutropenic colitis) CT of abdomen with contrast CT of abdomen with contrast Hepatic veno-occlusive disease Benign Pneumatosis intestinalis (VOD) Coy et al, Radiographics 2005 24 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 25 Zuzana Tothova, HMS III Gillian Lieberman, MD Acknowledgments: Gillian Lieberman, MD Maria Levantakis Senthil Palaniappun, MD Andrew Hines-Peralta, MD Suzana Zorca Paul Dieffenbach Larry Barbaras, Webmaster 26 Zuzana Tothova, HMS III Gillian Lieberman, MD References 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 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 Dietrich CF, Jedrzejczyk M, Ignee A. Sonographic assessment of splanchnic arteries and the bowell wall. European Journal of Radiology 2007; 64: 202-12 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 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 Shlomchik WD. Graft-versus-host disease. Nature Reviews Immunology 2007; 7:340-52
