造血干细胞移植后并发症影像学评估

1Zuzana Tothova, HMS III Gillian Lieberman, MD Radiologic Evaluation of Complications following Hematopoietic Stem Cell Transplantation Zuzana Tothova, HMS IIIZuzana Tothova, HMS III Gillian Lieberman, MDGillian Lieberman, MD 11/12/200711/12/2007 2Zuzana 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 3Zuzana 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 4Zuzana 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 5Zuzana Tothova, HMS III Gillian Lieberman, MD Outline of PBSCT: Critical to know 1. donor type 2. timing after SCT 3. extent of myeloablation & current immune status Shlomchik et al, Nat Rev Imm 2007 6Zuzana Tothova, HMS III Gillian Lieberman, MD Clinical factors to aid radiologic diagnosis: ƒWhat 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 ƒWhat conditioning regimen did the patient receive? • Full myeloablation: most autologous and allogeneic SCT • Non-myeloablative “mini-transplants”: allogeneic 7Zuzana Tothova, HMS III Gillian Lieberman, MD SCT type and timing affect nature of post-SCT complications Type Early complications (infectious, graft failure, VOD) Acute GVHD (acute, chronic) Autologous/Syng + - Allogeneic + + Myeloablative + + Non-myeloablative - + Chronic complications (infectious,auto immune ) - + + + Time (days) 30 1000 >100 8Zuzana Tothova, HMS III Gillian Lieberman, MD Let’s go back to our patient now… 9Zuzana Tothova, HMS III Gillian Lieberman, MD Our patient R.D. with fever: Chest radiograph PA Plain chest radiograph (PACS, BIDMC) 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 10Zuzana Tothova, HMS III Gillian Lieberman, MD Our patient R.D. with fever: CT of chest CT chest with contrast (PACS, BIDMC) ill-defined airspace opacities associated with: blood – pulmonary hemorrhage pus – pneumonia fluid – pulmonary edema nodule - tumor “Halo sign” associated with pulm hemorrhage Ground glass opacities associated with interstitial edema hemorrhage Pericardial effusion Pleural effusion 11Zuzana Tothova, HMS III Gillian Lieberman, MD Brief differential diagnosis ƒ Immunocompetent: (very broad) • Tumor • bronchoalveolar Ca • metastases - melanoma • Infection (pneumonia) • organizing pneumonia • eosinophilic pneumonia • atypical pneumonia • Inflammation (vasculitis) • Wegener’s ƒ Immunocompromised: • Infection • Infection • Infection CMV PCP Aspergillus TB any infection Rx: Voriconazole for presumed Aspergillus pneumonia 12Zuzana Tothova, HMS III Gillian Lieberman, MD Other presentations of Aspergillus in SCT patients: ƒ 2 forms of Aspergillosis CT chest w/o contrast Companion patient #1 (PACS, BIDMC) ƒ Not to be confused with Aspergilloma! • Tracheobronchial • Angioinvasive CT chest w/ (top) and w/o (bottom) contrast Coy et al, Radiographics 2005 13Zuzana 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 associated with Aspergillosis TB M. Avium CMV RSV CT chest with contrast (CAS, MGH) Rossi et al. RadioGraphics 2005 CT chest with contrast 14Zuzana Tothova, HMS III Gillian Lieberman, MD Other pulmonary complications of SCT ƒ CMV pneumonia ƒ Pulmonary complications occur in 40-60% SCT recipients ƒ Diffuse Alveolar Hemorrhage Coy et al, Radiographics 2005 ƒ pulmonary edema; PCP, VZV and Zygomyces pneumonia, etc. CT chest with contrast CT chest with contrast 15Zuzana 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… 16Zuzana Tothova, HMS III Gillian Lieberman, MD 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) 17Zuzana 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 non- bloody diarrhea, diffuse abdominal pain, NB/NB vomitting, decreased po intake secondary to nausea ƒWBC = 7.4, Neut = 82%, Lymph = 2% ƒ Supine plain abdominal film demonstrating no evidence of pneumoperitoneum or obstruction 18Zuzana Tothova, HMS III Gillian Lieberman, MD Our patient R.D.: diffuse bowel changes on CT CT abdomen and pelvis with contrast (PACS, BIDMC) Diffuse thickening of small and large bowel wall (4-5 mm) Featureless (loss of mucosal folds) Courtesy of Dr. Kruskal (BIDMC) Contrast study of GI Companion patient #3 19Zuzana Tothova, HMS III Gillian Lieberman, MD Halo of hypoattenuation within walls a.k.a. Target sign associated with Shock bowel Inflammation Vasculitis Pertinent negatives: No obstruction No perienteric/ pericolic fluid No pneumatosis CT abdomen with contrast (PACS, BIDMC) Our patient R.D.: diffuse bowel changes on CT 20Zuzana Tothova, HMS III Gillian Lieberman, MD Brief differential diagnosis ƒ Immunocompetent: (very broad) • Tumor (lymphoma) • Infection (enteritis) • Inflammation (Crohn’s) • Ischemia/vasculitis ƒ Immunocompromised s/p allogeneic SCT: Rx: Steroids for Acute GVHD GVHD GVHD GVHD Typhlitis Aspergillus, Candida Pseudomem. colitis 21Zuzana Tothova, HMS III Gillian Lieberman, MD 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! 22Zuzana Tothova, HMS III Gillian Lieberman, MD Menu of tests: additional imaging of GVHD ƒ U/S Doppler: F-FDG PET Ausberger et al, Transplantation 2007 Neumann et al, Gastrointestinal Endoscopy 2007 Dietrich et al, European Journal of Radiology 2007 ƒWireless capsule endoscopy: ƒ PET: 23Zuzana 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 Benign Pneumatosis intestinalisƒ Hepatic veno-occlusive disease (VOD) Coy et al, Radiographics 2005 24Zuzana Tothova, HMS III Gillian Lieberman, MD Summary of BMT-related complications Pre-engaftment (0-30 days) Early post-transplantation (30-100 days) Late Post-transplantation (100 days + ) Pulmonary edema DAH CMV pneumonia Idiopathic pulmonary syndrome Aspergillus Viral (non-CMV) & bacterial pneumonia Cryptogenic organizing pneumonia Constrictive bronchial obliterans Pulmonary proteinosis C. Difficile colitis Hepatic VOD Hemorrhagic cystitis (early) Hemorrhagic cystitis (late) Acute GVHD Chronic GVHD Adapted from Coy et al. RadioGraphics 2005 25Zuzana 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 26Zuzana 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 Slide Number 1 Slide Number 2 Slide Number 3 Slide Number 4 Slide Number 5 Slide Number 6 Slide Number 7 Slide Number 8 Slide Number 9 Slide Number 10 Slide Number 11 Slide Number 12 Slide Number 13 Slide Number 14 Slide Number 15 Slide Number 16 Slide Number 17 Slide Number 18 Slide Number 19 Slide Number 20 Slide Number 21 Slide Number 22 Slide Number 23 Slide Number 24 Slide Number 25 Slide Number 26