PGY3 Jaspreet Dhillon presented a case of 54 y/o F with history of CML and HTN presents with acute on chronic shortness of breath.  SOB started 8 months prior to admission and was treated with H2 blockers without resolution.  The SOB has worsened in the last 3 months along with dry cough, DOE and L sided pleuritic flank and back pain.  Denies fevers, night sweats, sick contacts or recent travel/immobilization. 

ROS: +15lb weight loss, +fatigue, +chest pain, rest per HPI

PMH: CML – diagnosed 2016

Home medications: Bosutinib 200mg qday, Loratadine 20mg qday

Social History: Lives at home with family in Los Angeles, No substance use.  Performs all ADLs at baseline.  Originally from Eritrea.

Vitals: T 36.7, HR 96, RR 33, BP 141/60, O2 sat 91% on RA

Physical Exam significant for non-toxic appearing female, +b/l nontender enlarged cervical LNs (immobile, firm), normal cardiac exam, +diffuse crackles bilaterally on pulm exam, no accessory muscle use on 2L NC, no hepatomegaly/splenomegaly, no b/l LE edema.

CBC: WBC 7.5> Hb 13.5/Hct 41 <Plt 207 (MCV 77.4, RDW 15.4%)

CMP:

Na 139/K 4.0/Cl 101/HCO3 27/BUN 18/Cr 0.63<Glucose 96

ALP 128>T.protein 8.1/Albumin 4.7/AST 28/ALT 21/Tbili 0.4/Dbili <0.2

Ca 10.3, Mg 2.0, Phos 2.9

Coags: PT 13.5, INR 1.04

AFB sputum bundle: AFB smear neg x3, MTB PCR neg x2

Quant Gold: Positive

HIV negative

Respiratory Culture: 4+ normal respiratory flora isolated

Fungal workup negative for Cocci, Crypto, Histo, Aspergillus and Blasto.

D-dimer: 2.02 (H)

LDH: 256 U/L (normal)

CXR: Innumerable b/l pulmonary nodules

CT Thorax: No pulmonary embolus.  Extensive pulmonary nodules within the lungs bilaterally with a diffuse random distribution.  Lytic lesions are noted in the manubrium. 

Left Supraclavicular nodule core biopsy: Metastatic Adenocarcinoma, favor a lung primary

Treatment: After biopsy resulted, the patient was discussed at Thoracic Tumor Board with decision to treat as lung cancer with erlotinib.  ID consulted for positive quant gold and she was started on INH monotherapy x 9months for latent TB treatment.  The patient was later switched from erlotinib to osimertinib. 

Teaching points:

1. CML: myeloproliferative disorder, 90% of adults with BCR-ABL translocation.  Imatinib was the first TKI developed for CML and later due to resistance, several alternative TIKs have been developed: Erlotinib, dasutinib, bosutinib, nilotinib.
2. Toxicities of TKIs:
   1. Cardiac: QTc prolongation, fluid retention, CHF
   1. GI: GI distress, GI bleeding, elevated hepatic enzymes, pancreatitis
   1. Renal: injury in 22% with imatinib, <10% with  bosutinib
   1. MSK pain and cramps
   1. Derm: pruritus, acneiform rashes, hyperpigmentation
   1. HA
   1. Endocrine: hyperphosphatemia, thyroid hormone alterations
   1. Pulm: ILD, pleural effusions, PAH

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