Hematopoietic Cell Transplant (HCT) Case Scenarios for

Referring Providers

Dr. Monica Bhatia, Columbia University Medical Center

Dr. Fawwaz Khalid Yassin, Sheikh Khalifa Medical City

Outline

• Recognize which patients need to undergo a hematopoietic cell transplant (HCT)• Understand the expected clinical course of a HCT• Recognize timeline of complications• Treatment of complications based on when they occur

Who needs a HCT?•Malignancies• Allogeneic• Autologous

• Bone Marrow Defects:• Sickle Cell and Thalassemia• Bone Marrow Failure Syndromes• Aplastic Anemia

• Immune Deficiencies or Dysregulation • HLH• Primary Immune Deficiencies – SCID, Chronic Granulomatous

Disease, Wiskott-Aldrich, others

Timeline of HCT Complications

Engr

aftm

e

nt

Day

OConditioning

Pancytopenia

Post Engraftment

Conditioning Intensities

Myeloablative

• More intense

• Higher toxicities and more complications

• Hematopoiesis completely ablated and irreversible

• Used for Malignancies and diseases with difficult engraftment

Reduced Intensity

• Less intense

• Goal is fewer toxicities

• More mixed chimerism

• Can eventually have autologous recovery

• Used for some Non-malignant diseases and patients that can’t tolerate myeloablative

Timeline of HCT Complications

Day

O

Engr

aftm

e

ntConditioning

Pancytopenia

Post Engraftment

What to look for:• Nausea/Vomitin

g• Side effects of

MedicationsInfusional Reactions:• Anaphylaxis• DMSO toxicity• Hypertension

Pancytopenia

Day O

Engr

aft

Pancytopenia:

• Transfusions• Infections – bacterial,

fungal*• Mucositis• Intubation• Diarrhea• Pain and Nutritional

Management

BMT Specific Side Effects:• VOD – Veno-Occlusive Disease

• TMA – Transplant Associated Microangiopathy

• PRES – Posterior Reversible Encephalopathy Syndrome

Case 1

• Baby G is a 6mo infant with HLH receiving an HCT from an older sibling. • He is D+3 after receiving a myeloablative conditioning

regimen with Busulfan and Cyclophosphamide• You are called to the bedside due to increased work of

breathing (RR70s)• He is afebrile but tachycardic (HR180)• CXR is normal but on your exam you hear transmitted

upper airway noise and note copious thick secretions

•MUCOSITIS

Case 2

• Little Mary is a 6yo with refractory ALL undergoing an unrelated donor HCT. • She has received myeloablative conditioning with TBI

and Cyclophosphamide• She engrafted on D+18 and was doing well but you’ve

noticed that her weight has increased every day for the past few days. • She is now D+21, her weight is 20kg (baseline 14kg)

and she has new complaints of abdominal pain and increased work of breathing• What should you be concerned about?

Veno-occlusive Disease (VOD)• Occurs in upwards of 30% of HCT (dependent on prior liver injury and

conditioning regimen)

• Often occurs between D10 – D28

• Criteria:• Weight Gain• Elevated Bilirubin (*can have normal bilirubin)

• Tender Hepatomegaly (RUQ pain)• Reversal of flow on Doppler US• *platelet refractory

• *change in metabolism of medications (ie. Tacrolimus levels)

• Management:• Defibrotide• Ursodiol for prophylaxis• Drains and CRRT

Case 3• Jay is a 12yo with Sickle Cell Anemia receiving an HCT from

an unrelated donor. • He has a history of a stroke at the age of 3y and had

multiple episodes of Acute Chest Syndrome in the past. • He is now D+18 from his myeloablative transplant and he

recently began complaining of headaches. • He is receiving cyclosporine/MTX for GVHD ppx• He seems okay after Tylenol but you notice his BP is higher

than usual, at 145/90. • You’re called to the bedside after he begins having a Seizure

Posterior Reversible Encephalopathy Syndrome (PRES)• Incidence: 1-10% of HCT• Higher risk in patients with Calcineurin Inhibitors, Sickle Cell, aGVHD• Clinical Presentation:• Headaches• Vomiting• Change in Mental Status/Encephalopathy• Seizures• Rarely can cause edema and herniation

• MRI• Management:• Supportive Care, seizure management• Change Immune Suppression

Case 4• Julie is 5yo with high risk neuroblastoma who is receiving high

dose chemotherapy and autologous stem cell rescue• She is D+28 after autologous HCT and she appears to be fully

engrafted• However, she continues to be slightly anemic and require platelet

transfusions every other day• She has also required increasing doses of anti-hypertensive

medications, now on Amlodipine, Clonidine, and Enalapril but BP remains elevated at 160/85. • You are called for management of hypertensive urgency• On labs, her creatinine has increased from 0.2 to 0.6 and UA

shows evidence of proteinuria

Transplant Associated Thrombotic Microangiopathy (TMA)• Endothelial damage leading to an HUS type picture• Occurs in 10-35% of HCT• Still not well understood• Criteria/Symptoms

• Hemolytic Anemia (elevated LDH, schistocytes)• Thrombocytopenia• Renal involvement elevated creatinine, UA with proteinuria• Significant and difficult to control hypertension• Can have intestinal symptoms(pain, diarrhea, GI bleed), lung involvement

(pulmonary HTN), effusions (pericardial or pleural)

• Terminal Complement Activation – elevated C5b-9 or CH50• Management:

• Eculizumab – blocks terminal complement activation• Steroids, plasmapheresis variable efficacy

Timeline of HCT Complications

Day

O

Engr

aftm

e

ntConditioning

Post Engraftment

What to look for:• Nausea/Vomiting• Side effects of

MedicationsInfusional Reactions:• Anaphylaxis• DMSO toxicity• Hypertension

Pancytopenia

Peri-Engraftment:• Engraftment

Syndrome• Idiopathic Pneumonia

Syndrome

ANC > 500 for 3 days

Cord “naïve” = 21-28dPBSC “mature” = 10-14dBM “middle” = 14-21d

Case 5

• Rachel is a 9yo with relapsed AML receiving a matched sibling HCT• She received a bone marrow transplant from her older

brother• She started with high fevers yesterday to 40oC that

respond to Tylenol but recur when Tylenol wears off• She is D+16 today and her labs now shows and ANC of

100, with an AST of 120 and ALT of 103• She has a faint erythematous rash on her trunk• She is otherwise well appearing, vitals only significant

for fever, tachycardia with fever, and BP of 120/50 and weight increased by 2kg

Engraftment Syndrome• Wide range of incidence: 7-59%• Thought to be related to cytokine release• Clinical presentation:• Fevers• Rash• Vascular Leak• Organ dysfunction (increased transaminases, creatinine)

• Management:• Supportive• Steroids

Case 6• David is 15yo male with relapsed ALL who received a

myeloablative HCT from his sister• He is D+16 and not yet engrafted. • He started complaining of trouble breathing and RR

increased to 30, pox in low 90s last night. • He worsened overnight and when you arrive this morning,

you find him on 15L by facemask, RR45, and only able to speak in short phrases. He is afebrile.• CXR is without consolidation but shows diffuse infiltrates• PICU is called for concern for impending respiratory failure

Idiopathic Pneumonia Syndrome• Incidence 2-12% • Due to inflammation/cytokine storm, TNFα implicated• Clinical presentation:

• Often rapid, around time of engraftment• Respiratory distress• CXR with diffuse infiltrates• Clinical course rapidly progress from O2 • requirement requiring intubation, oscillation

• Management:• Manage respiratory symptoms as needed• Rule out infection BRONCHOSCOPY• Steroids and TNFα inhibition with Etanercept

Timeline of HCT Complications

Day

OConditioning

Post Engraftment

What to look for:• Nausea/Vomiting• Side effects of

MedicationsInfusional Reactions:• Anaphylaxis• DMSO toxicity• Hypertension

Pancytopenia

Peri-Engraftment:• Idiopathic Pneumonia

Syndrome• Engraftment Syndrome

Engr

aftm

e

nt

Post Engraftment

Graft Versus Host Disease:• Acute • Chronic

Infections:• Viruses• Post Transplant

Lymphoproliferative Disease

• If prolonged immunosuppression – fungus

Relapse

Graft Versus Leukemia

Acute Graft Versus Host Disease: <D100• Occurs in 30-50% of HCT, severe in about 14%• Suggests graft-versus- leukemia effect• But associated morbidity and mortality

SKIN

Gut Liver

Chronic Graft Versus Host Disease: After D100

• Immune Dysregulation – similar to autoimmune syndromes• Skin – eczematous to

sclerodermatous• Liver – chronic cholestatis, “vanishing

bile ducts”• Gut – like IBD, strictures and

malabsorption• Pulmonary – restrictive or obstructive • Hematologic – hemolytic anemia,

thrombocytopenia• Mouth • Eyes – Sjogren’s-like

Infections

Neutropenia = bacteria, fungi

Lymphopenia = viruses• Adenovirus• CMV• EBV• VZV• BK virus

Chronic Immune Suppression = Aspergillus, viruses

Post Transplant Lymphoproliferative Disease• Risk Factors:• T-cell depleted grafts (ie. CD34+ selection)• Use of ATG or Campath

• Clinical Presentation:• Lymphadenopathy• Increasing EBV viral load

• Management:• Decrease or stop immune suppression• Give Rituximab• If refractory – EBV-specific cytotoxic T-cells

Questions?