covid vaccines 1/28/2021, 2/18/2021, and 10/29/2021, all pfizer, had rapid decline and progression of dyspnea and profound cytopenias 1 wk after booster, ultimately dx'd w/ MDS-U, hypoplastic, on tx, all seemed to rapidly decline 1 wk post booster  Patient is a 70 y.o. male with bone marrow failure, who has been referred for consultation regarding allogeneic transplant. He presented to outside hospital on 11/12/21 with right sided paraesthesia, and was found to have a left subarrachanoid frontal lobe hemorrhage.  He was profoundly cytopenic at presentation, with a plt count of 4, hgb of 7, and WBC of 1.8.  He has been very active throughout his life, and was riding his bike 60 miles a week.  He felt that his endurance started to decline around a month prior to presentation.   He did not require surgical intervention for his bleed, and was managed with aggressive platelet transfusions.   He had a bone marrow biopsy on 11/12/21 which showed a hypocellular marrow (10%), with severely decreased hematopoiesis, no dysplasia, and numerous small mature lymphocytes.  NGS unremarkable and cytogenetics showed isolated 13q deletion. Repeat bone marrow bx on 11/23/21 showed an aplastic marrow without dysplasia.   He received a trial of IVIG and dexamethasone x 4 days with no response.  He started hATG x 4 days, promacta, cyclosporin and prednisone on 11/25.  Outpatient promacta currently on hold pending medication copay assistance.   He feels well today and has no acute complaints.  No new neurological complaints or headaches.  Denies any infections symptoms.       Cancer Staging No matching staging information was found for the patient.             Diagnosis:  MDS   APPOINTMENT:   12/2/21 Dr.  REFERRING PHYSICIAN: Dr.  Allergies: Penicillins and Sulfa (sulfonamide antibiotics)  Family Hx: Father:  Bone Cancer  (Deceased) Mother/Mat. Grandmother: Alzheimer's(Both deceased), GPA/MPA father, hashimoto's thyroiditis daughter, henoch-schonlein purpura daughter He has 2 brothers, age 75 and 58.  Two daughters age 35 and 31.   Medical Hx: Essential HTN, GERD, a fib, iron deficiency anemia, hypothyroidism, prediabetes, ED Surgical Hx: Cardiac ablation (10/30/20), colonoscopy, knee replacement, upper GI endoscopy, s/p placement of implantable loop recorder. Social Hx:  Married, retired school superintendent, former smoker (1ppd; 7 pack-years) quit at age 26, ETOH use, no current drug use Patient is a 70 y.o.  gentleman with a PMH for hypertension, hypothyroidism, atrial fibrillation s/p ablation in 2020 who presented to Facility following right-sided paresthesias.  Patient reported experiencing mild headaches and significant decrease in energy which is unusual because he is very athletic. Lab work at Facility indicated patient was pancytopenic with a platelet count of 4K.  He was transferred to higher level of care for further evaluation. Patient was found to have profound thrombocytopenia, anemia, concerning for aplastic anemia. Ultimately, patient was transferred to inpatient hematology to begin treatment.  Patient underwent a BMBX on 11/12/21 that showed markedly hypocellular bone marrow (10%) with near absent trilineage hematopoiesis, less than 1% blasts, and numerous small mature lymphocytes in the aspirate smears. FISH was negative. Repeat BMBX indicated markedly hypocellular bone marrow (<5%) with nearly absent trilineage hematopoiesis and 1% blasts.  Due to concern for aplastic anemia with ongoing frequent transfusion requirements, patient started hATG x 4 days, eltrombopag, cyclosporine, and prednisone on 11/25.  Patient presents today following hospital discharge for follow-up. Timeline of Events:     Aplastic anemia (HCC)   11/10/2021 Imaging     CT LMH Small amount of subrachnoid hemorrhage of uncertain etiology overlying the high left frontal lobe posteriorly.     11/12/2021 Pertinent Labs     LMH WBC: 1.8 RBC: 2.22 HGB: 7.0 HCT: 19.5 PLT: 4 ANC: 162     11/12/2021 Pertinent Labs     WBC: 0.8 RBC: 1.40 HGB: 4.4 HCT: 12.9 RDW: 15.1 PLT: 82 ANC: 0.11 Lymphocytes:  82     A. Peripheral blood, flow cytometry:  Minor PNH clone identified in both WBCs and RBCs.   Interpretation:  Flow cytometric analysis shows a minor PNH clone within the granulocytes  (0.25%), monocytes (0.07%) and a minor PNH clone in the RBCs (0.04%). The clinical significance of the small populations with GPI deficiency is uncertain. Small PNH clones have been reported in cases of myelodysplastic syndrome and aplastic anemia.     11/12/2021 Biopsy     BMBX KU Bone marrow, left iliac crest, aspirate, biopsy, clot, and touch prep:  Markedly hypocellular bone marrow (10%) with near absent trilineage hematopoiesis, less than 1% blasts, and numerous small mature lymphocytes in the aspirate smears.    Peripheral blood smear:  Pancytopenia with severe normocytic anemia, leukopenia with neutropenia, and marked thrombocytopenia.    Flow cytometry: Bone Marrow, flow cytometry:  Negative phenotypic study.    Cytogenetics:  46,XY,del(13)(q14q22)[cp3]/46,XY[12] FISH:  NGS:  Pending   TP53 PCR Array:  Not Detected      11/12/2021 Imaging     X-ray-Chest KU No consolidation or pleural effusion.      11/12/2021 Imaging     CTA Head  1.  Mild increase in subarachnoid hemorrhage at the left frontal lobe.  2.  No intracranial arterial stenosis, aneurysm, vascular malformation, or large vessel occlusion identified.  3.  Very mild white matter disease, likely secondary to chronic microvascular ischemic changes.      11/12/2021 Imaging     MRI Head  MR brain:   1.  Stable localized subarachnoid hemorrhage along the left frontal cerebral convexity (superimposed superficial siderosis could also be present). Superimposed linear leptomeningeal enhancement, likely reflecting incidental reactive benign vascular engorgement, though, conventional cerebral arteriogram may be beneficial to exclude subtle arteriovenous malformation-fistula.  2.  Mild patchy supratentorial white matter FLAIR hyperintensities, likely due to chronic microvascular ischemic changes.  3.  Small right mastoid effusion.    MRV brain:  Normal MRV of the brain.      11/17/2021 Pertinent Labs     Peripheral Blood A. Peripheral blood, flow cytometry:  Negative immunophenotypic study.      11/23/2021 Biopsy     BMBX KU  Bone marrow, left iliac crest, aspirate, biopsy, clot, and touch prep:  Markedly hypocellular bone marrow (<5%) with nearly absent trilineage hematopoiesis and 1% blasts.    Peripheral blood smear: Pancytopenia  Comment:  Rare erythroid and myeloid elements are present for evaluation.  Megakaryocytes are absent. There is no morphologic evidence of dysplasia or increase in blasts. The presence of deletion of 13q in the previous marrow is noted. The overall morphologic and cytogenetic findings are consistent with myelodysplastic syndrome, unclassifiable (hypoplastic myelodysplastic syndrome).    Flow cytometry: Not done Cyto/FISH: Not done       11/29/2021 Imaging     CT Head WO Contrast  1.  Decreased conspicuity of left frontal subarachnoid hemorrhage. No new areas of hemorrhage identified.  2.  Mild patchy supratentorial white matter hypodensities, likely sequela of chronic microvascular signal changes.         11/30/2021 Pertinent Labs     WBC: 0.3 RBC: 2.23 HGB: 7.1 HCT: 19.5 RDW: 15.3 PLT: 26 BUN: 15 Creat: 0.73 Alb: 3.5 Ca: 8.0 TP: 6.5 Tbilli: 2.   Review of Systems  Constitutional: Positive for activity change.  HENT: Negative for congestion.   Eyes: Negative.   Respiratory: Positive for shortness of breath (exertional).   Cardiovascular: Negative for leg swelling.  Gastrointestinal:       Heartburn   Skin: Positive for pallor.  Allergic/Immunologic: Positive for immunocompromised state.  Neurological: Positive for headaches (mild, intermittent.  None today ). Negative for speech difficulty.  Hematological: Bruises/bleeds easily.  Psychiatric/Behavioral: Negative for agitation and confusion.      Objective:        ? acetaminophen (TYLENOL EXTRA STRENGTH) 500 mg tablet Take 500 mg by mouth every 8 hours as needed for Pain. Max of 4,000 mg of acetaminophen in 24 hours. ? acyclovir (ZOVIRAX) 800 mg tablet Take one tablet by mouth twice daily. Indications: infection prophylaxis, medical ? amLODIPine (NORVASC) 5 mg tablet Take one tablet by mouth daily. ? calcium carbonate/vitamin D-3 (OSCAL-500+D) 1250 mg/200 unit tablet Take 1 tablet by mouth daily. Calcium Carb 1250mg delivers 500mg elemental Ca ? cycloSPORINE modified (CYCLOSPORINE) 100 mg capsule Take two capsules by mouth twice daily. Take with one 25 mg capsule for a total of 225 mg twice daily.  Indications: Aplastic Anemia ? cycloSPORINE modified (CYCLOSPORINE) 25 mg capsule Take one capsule by mouth twice daily. Take with two 100 mg capsules for a total of 225 mg twice daily.  Indications: Aplastic anemia ? eltrombopag (PROMACTA) 75 mg tablet Take two tablets by mouth daily. Take on an empty stomach, at least 1 hour before or 2 hours after food.  Separate from antacids by at least 4 hours. ? fluconazole (DIFLUCAN) 200 mg tablet Take two tablets by mouth daily. Indications: infection prophylaxis, medical ? levoFLOXacin (LEVAQUIN) 750 mg tablet Take one tablet by mouth daily. Indications: infection prophylaxis, medical ? levothyroxine (SYNTHROID) 88 mcg tablet Take 88 mcg by mouth daily. ? melatonin (MELATIN) 5 mg tablet Take 5 mg by mouth at bedtime daily. ? multivitamin with minerals (MULTIVITAMIN & MINERAL FORMULA PO) Take 1 tablet by mouth daily. ? omeprazole DR (PRILOSEC) 20 mg capsule Take 20 mg by mouth daily before breakfast. ? predniSONE (DELTASONE) 10 mg tablet Take seven tablets by mouth daily for 4 days, THEN 5.5 tablets daily for 3 days, THEN 3.5 tablets daily for 3 days, THEN two tablets daily for 3 days, THEN one tablet daily for 3 days. ? sildenafil (REVATIO) 20 mg tablet Take 1-3 tablets by mouth as Needed. ? trimethoprim/sulfamethoxazole (BACTRIM DS) 160/800 mg tablet Take one tablet by mouth twice daily twice weekly. Take AM and PM on Mondays and Thursdays only  Indications: infection prophylaxis, medical     BP 125/71 (BP Source: Arm, Left Upper, Patient Position: Sitting)  | Pulse 93  | Temp 36.5 °C (97.7 °F) (Oral)  | Resp 16  | Wt 72.1 kg (159 lb)  | SpO2 100%  | BMI 22.81 kg/m²  Wt Readings from Last 5 Encounters: 12/08/21 72.1 kg (159 lb) 12/07/21 71.2 kg (156 lb 14.4 oz) 12/05/21 71.9 kg (158 lb 9.6 oz) 12/04/21 71.2 kg (157 lb) 12/02/21 71.3 kg (157 lb 3.2 oz)   Body mass index is 22.81 kg/m².    Pain Score: Zero   Fatigue Scale: 4   Pain Addressed:  N/A   Karnofsky Scale: 70% Cares for self; unable to do normal activity, or active work  BMT Assessment & Plan   Diagnosis: MDS-U Cytogenetics: 13q deletion NGS: No variants detected High Risk - R-IPPS 5 at diagnosis      Patient is a 70 y/o male with bone marrow failure due to MDS-U with 13q deletion. His clinical course has been complicated by a subarachnoid hemorrhage due to severe thrombocytopenia, from which he has now clinically recovered.  He is being treated with triple IST with hATG, cyclosporin and promacta (staring 11/25/21), based on a retrospective study.   He has had no response so far, remains profoundly pancytopenic and requiring transfusions multiple times a week.   He has high risk MDS per R-IPSS, and we now have prospective randomized data from BMT CTN 1102 which shows a clear survival benefit in patients with intermediate and high risk MDS.  I discussed the case in BMT multi-disciplinary conference, and this was the consensus recommendation.  I discussed the logistics, adverse effects associated with allo-HCT, and patient wants to proceed with transplant workup.   Patient has been HLA typed and a donor search is ongoing.   Cyclosporin level being managed per pharmacy    Heme:  Transfuse for hgb < 7, plt < 10 (inpatient), plt < 20 (outpatient).   Recent subarachnoid hemorrhage.  Plt transfusion to be given 12/8/21 - Restart eltrombopag 150 mg qday as soon as medication copay assistance approved    Upon physical exam, patient  currently meets criteria to exceed standard TACO rates     Endo:  Started on prednisone taper inpatient as part of IST.  On taper to finish on 12/17/21.  Closely monitor glucose.     Infectious disease:  Remains profoundly immunosuppressed.  On ppx with acyclovir, fluconazole, levofloxacin, bactrim.     Subarachnoid hemorrhage -Observed on CT head prior to admission, Concern for dAVF on CTA and MRI -Cerebral angiogram on 11/16 without any evidence of AVM, dAVF, or aneurysm -No indication for neurosurgical intervention at this time -S/p Keppra 11/12 through 11/19 -Repeat CT head 11/29 mild resolution of previously seen SAH, no new intracranial hemorrhage. Plan: > Follow-up with neurosurgery with repeat imaging on 12/12 >Amlodipine discontinued by nephrology on 12/7/21. Patient to monitor blood pressures at home. If SBP consistently > 140, restart amlodipine given recent SAH.   FEN/Renal:  - Mild hyponatremia.  Being managed by nephrology, seen on 12/7/21     HTN > Titrate amlodipine to SBP < 140   Hypothyroidism -PTA levothyroxine 88 mcg, continuing during admission   History of A. Fib -S/p ablation 2020 -Previously on Eliquis but discontinued after 3 months   RTC:  Labs 3x a week (due to transfusion needs).  Provider weekly