CC: Two episodes of speech difficulty and right sided weakness

HPI: MK is a 49 yo RH WM with Hx of acute promyelocytic leukemia (APL) dx 9/98 s/p chemotherapy apparently in remission by negative BMBx 2 months ago. Other than a mild URI 3/29, he was in his USOH, until five days PTA, on the way to work, he suffered acute speech arrest, R arm and leg weakness. He sought no medical attention at that time, and went back home where he slept it off, apparently resolving on its own six hours later. He suffered a more severe episode one day PTA, when he collapsed to the ground without loss of consciousness while working on his boat. He was brought to an OSH by EMS where evaluation noted improving symptoms of R facial droop, R arm/leg weakness and aphasia. He was transferred to BJH for further management.

PMH:

• APL dx'd 7 months ago initially presenting as gingival bleeding and easy bruising. Received idarubicin with ARA-C as induction chemotherapy, followed by ATRA. Developed ATRA syndrome x 2 requiring discontinuation. He subsequently received anthracycline consolidation x 4 weeks, 6 weeks PTA. Treatment course c/b multiple platelet transfusions, and two Hickman catheter infections.
• Borderline HTN, no meds. no CAD, no DM.

Meds: none

SHx: quit tobacco 11 years ago, and does not drink. Lives with his family and is a police captain.

FHx: 2 sisters, and 2 children who are all healthy, M and F with CAD, mGM with stroke.

ROS: (+) dull retro-orbital dull headache, nonproductive cough.

PE 36.5 88 20 150/80

Gen: robust man in NAD. HEENT: no gingival bleeding. Neck: supple without bruits, L side of neck tender to palpation, Lungs: clear bilaterally. Heart: RRR no m/r/g Abd: soft NT, ND obese. Extr: no C/C/E. Skin: no ecchymoses

Neuro: MS: A + Ox3, naming, repetition, reading, comprehension intact. CN: VFFTC, EOMF, ny nystagmus, discs flat, fundi benign, P 6->3 ERRL, V1-3 intact to LT/PP, Face had ? decreased RNLF, hearing intact palate upgoing bilaterally, mod gag, TML, Traps 5/5. Motor: slight pronation of R on Barre, decreased FFM on R, slight orbiting of R arm, normal tone and bulk, 5/5 in formal strength testing. Sensory: LT/PP/JPS/intact, slight symmetric vibratory sense loss in LEs. No extinction to DSS. Coord: FNF HKS RAM intact DTR: slightly brisk 3+ bilaterally, toes downgoing. Gait: normal, negative Romberg

OSH studies: initial noncontrast head CT: within normal limits. WBC 8800 (57S 24L 16M 3E) Plt 94,000/ml, Hgb 11.4/ Hct 32.7 PT 12.7 PTT 22. ESR 34. EKG LVH.

Localization: L MCA territory

DDx: Infection, ATRA syndrome, CNS relapse of leukemia, Ischemic stroke (stroke risk factors, male, tobacco, HTN), Venous infarct

Hospital course:

• By morning, exam was normal. Treatment? Per Heme/Onc: Okay to give ASA. (given).
• Echo: LAE, no WMA, nl LV fcn, no thrombus.
• Carotids: < 50% stenosis bilaterally,
• Head MRI: leptomeningeal enhancement in L occipital region, extending to the midline cerebellum, increased FLAIR in correspinding regions c/w leptomeningeal carcinomatosis vs. meningitis. No DWI abnormalites to suggest infarction. Bilateral sphenoid and R max sinus dz. HIV (-), Chol 225 fTG 353 HDL 26 LDLc 128.
• LP: CSF protein 110 glucose 50 total cells 3218 nucleated 2129 Diff (1%L 5%N, 4%B, 1%myelo, 14%promyelo, 75%blasts) Cultures/stains(-) Crypto (-)
• BMBx: negative for leukemic cells
• PCR for PML-RARa T(15:17) (result not available)
• On 4/8 he was transferred to the BMTx service, enrolled in the arsenic protocol (x 28 days) and received intrathecal MTX/ARA-C/Hydrocortisone (x2). He had increased bleeding time (normal PT/PTT) which was attributed to ASA x 2 days (normal vWF). He was discharged and then rescheduled to have an Ommaya reservoir placed for chemotherapy.
• On 4/16 his scheduled day of admision, he was readmitted with same recurrent TIA symptoms. That day, he underwent Ommaya placement and ventricular catheter in frontal horn of the R lateral ventricle. Three hours post-operatively, he developed left sided weakness, but was following commands. A Stat CT of the head showed no hemorrhage. Neurology consultation's impression was dystonic posture on the left and behavioural changes, each thought to be secondary to compazine (10 mg the night before) and to versed (10 mg given at time of head CT), resepectively, but to consider angiogram to look for vasculitis if symptoms recurred. He underwent whole brain radiation. and has been admitted multiple times for continued arsenic treatment and intrathecal MTX/ARA-C/Hydrocortisone.

Leuk Lymphoma 1999 Apr;33(3-4):219-29
Extramedullary disease in acute promyelocytic leukemia.
Evans GD, Grimwade DJ
Department of Haematology, Addenbrooke's Hospital, Cambridge, UK.

All-trans retinoic acid (ATRA) is currently recommended as standard treatment for acute promyelocytic leukemia (APL). However there has been increasing concern that ATRA is associated with unusual sites of relapse. Although there is insufficient evidence so far to substantiate this, we review the potential mechanisms by which ATRA may increase the incidence of extramedullary and, in particular, central nervous system (CNS) relapse.
PMID: 10221502, UI: 99236691

ATRA syndrome and thrombotic events

Leuk Lymphoma 1996 Feb;20(5-6):435-9
Thrombosis in patients with acute promyelocytic leukemia treated with and without all-trans retinoic acid.
Escudier SM, Kantarjian HM, Estey EH
Department of Hematology, Leukemia Section, University of Texas M.D. Anderson Cancer Center, Houston, USA.
Laboratory evidence of disseminated intravascular coagulation (DIC) and/or fibrinolysis is present in the majority ofpatients with acute promyelocytic leukemia (APL). Historically, early hemorrhagic death (EHD) occurred in 10% to30% of patients treated with chemotherapy. All-trans retinoic acid (ATRA), a differentiating agent, has a CR rateabove 80% in patients, with ATRA-associated leukocytosis. We studied thrombotic events in this population andcompared it to patients treated with chemotherapy alone. The results of studies using ATRA in patients with APL werereviewed. Patients received ATRA 45-50 mg/m(2) orally in two divided doses daily until complete remission. Innewly diagnosed patients, Idarubicin 12 mg/m(2)/day was given intravenously for 4 to 5 days beginning on the fifthday of ATRA therapy or when the white blood cell count (WBC) was over 10x 10(3)/mu l. Thrombotic complicationswere noted in 3 of 31 patients during induction. Two died from thrombotic events during therapy with multiplethromboses documented at autopsy. ATRA syndrome was suspected in 2 of the patients with thromboses and only 1 ofthe patients without thrombosis. In previous studies, 1 of 25 APL patients treated with chemotherapy alone hadthrombotic events during therapy. In conclusion, treatment of APL with ATRA may decrease the incidence ofhemorrhagic complications, but does not eliminate thrombosis. While thrombotic events were not significantlyincreased in patients treated with ATRA, they were more common in patients suspected of having ATRA syndrome.
Publication Types:
Clinical trial
PMID: 8833399, UI: 96430273

ATRA syndrome