Sex: F
Vaccine: COVID19
Symptoms: Coombs direct test, Cryoglobulins, Eosinophil count, Flow cytometry, Fluorescent in situ hybridisation
Clinical narrative: COVID-19 PNEUMONIA; ACUTE RESPIRATORY FAILURE; ACUTE MYELOID LEUKEMIA (AML); SCLERODERMA; SJOGREN'S SYNDROME; SUSPECTED CLINICAL VACCINATION FAILURE; CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML); This spontaneous report was received from company representative via social media (traditional media report) and from other health professional via literature: This report concerned a 74 year old female of unspecified race and ethnicity. The objective of this study was to present a rare case of CMML (chronic myelomonocytic leukemia) after receiving the J and J COVID-19 vaccines, in association with limited scleroderma. The patient's height, and weight were not reported. The patient's concurrent conditions included: asthma, hypertension, dyslipidemia. On an unspecified date in OCT-2020, Laboratory data included: Absolute neutrophil count (NR: 1.7 - 7) 3.7 10x3/uL, Eosinophils (NR: 0 - 0.5) 0.2 10x3/uL, Hematocrit (NR: 34.9 - 44.5) 35.8 percent, Hemoglobin (NR: 12 - 15.5) 11.8 g/dL, Lymphocytes (NR: 0.9 - 2.9) 1.8 10x3/uL, Monocytes (NR: 0.3 - 0.9) 0.6 10x3/uL, Platelet count (NR: 150 - 450) 199 v10x3/uL, Red blood cell count (NR: 3.9 - 5.03) 3.77 10x6/uL, Reticulocyte count (NR: 0.5 - 1.5) not reported, and White blood cells (NR: 4.4 - 11) 6.3 103x/uL.  The patient received covid-19 vaccine ad26.cov2.s (suspension for injection, route of admin, and batch number were not reported, expiry: unknown) dose was not reported, 1 total, administered on 08-MAY-2021 for prophylactic vaccination. The batch number was not reported and has been requested. No concomitant medications were reported.  On an unspecified date, the patient presented to the emergency department with complaints of shortness of breath and generalized weakness for two days. The patient reported that symptoms began after receiving the first dose of the Johnson and Johnson vaccine for COVID-19. Patient was hemodynamically stable with a heart rate of 94, a respiratory rate of 21, and a saturation rate of 99 percent on room air. Physical examination was widely unremarkable except for decreased air entry with mild diffuse wheezes bilaterally on lung auscultation. No cyanosis or edema of the extremities. On 12-MAY-2021, Laboratory data included: Absolute neutrophil count 3.9 10x3/uL, Eosinophils 0.1 10x3/uL, Hematocrit 29.5 percent, Hemoglobin 9.9 g/dL, Lymphocytes 3.8 10x3/uL, Monocytes 11.5 10x3/uL, Platelet count 37 10x3/uL, Red blood cell count 3.01 10x6/uL, Reticulocyte count not reported, and White blood cells 19.4 10x3/uL. On 18-JUN-2021, Laboratory data included: Absolute neutrophil count 9.6 10x3/uL, Eosinophils 0.0 10x3/uL, Hematocrit 20 percent, Hemoglobin 6.8 g/dL, Lymphocytes 5.5 10x3/uL, Monocytes 19.1 10x3/uL, Platelet count 10 10x3/uL, Red blood cell count 1.99 10x6/uL, Reticulocyte count 1.9 percent, and White blood cells 34.5 10x3/uL. On 12-MAY-2021, patient presented with anemia, thrombocytopenia, and leukocytosis after the COVID-19 vaccine. The hepatitis panel and human immunodeficiency virus were negative. The thrombocytopenia was concerning for vaccine-related immune thrombocytopenic purpura (ITP). The patient received a tapering dose of steroids and two doses of intravenous immunoglobulin (1 g/kg) as a treatment for ITP, with only a transient rise in platelets. On further follow-up, platelets continued to trend down, even refractory to steroids. Eventually, the patient developed transfusion-dependent thrombocytopenia. Patient also started complaining of dry mouth, difficulty swallowing, and new-onset episodes of whitish discoloration of the fingers in cold temperatures. Patient had concomitant CMML and scleroderma, which were unmasked after the patient received the COVID-19 vaccine and patient had scleroderma with elevated centromere 2b antibodies and the symptoms of difficulty swallowing and Raynaud's phenomenon.  On an unspecified date, the patient had Sjogren's syndrome with elevated anti-SSA and dryness of the mouth. Rheumatologic workup was positive for anti-centromere antibodies and Sojgren's anti-SSA (anti Sjogren's-syndrome-related antigen A autoantibodies). C-ANCA, P-ANCA (Antineutrophil Cytoplasmic Antibodies), RF (Rheumatoid factor), anti-SSB, and anti-scleroderma 70 were negative. Cryoglobulin, cold agglutinin, and direct coombs were also negative. On follow-up, it was observed that the patient was progressing to severe anemia and leukocytosis with persistently high and up-trending monocytes. Flow cytometry on peripheral blood and bone marrow biopsies was done to rule out leukemia. Bone marrow biopsy results were significant for chronic myelomonocytic leukemia stage 0 (CMML 0) in a hypercellular marrow. The blasts and promonocytes were not increased; in the setting of severe anemia and thrombocytopenia with monocytosis (AMC 12.6 K/µL - 53.8 percent of total leucocytes) was consistent with CMML 0. Next-generation sequencing detected KRAS (Kirsten rat sarcoma viral oncogene homolog), NPM1 (nucleophosmin gene), and TET2 (Tet methylcytosine dioxygenase 2) gene variations, and karyotyping showed 46, XX female karyotypes. Flow cytometry showed monocytosis (60 percent) and dysgranulopoiesis with no increased blasts or lymphoproliferative disorder. There is no increase in CD34-positive myeloblasts, and they comprise 0.4 percent of the total cells. The monocytes (60 percent) are increased with decreased CD13 and CD14 and increased HLA-DR (Human leukocyte antigen), suggesting left-shifted maturation. The granulocytes (19 percent) show decreased side scatter, suggesting hypogranularity with left-shifted CD13/CD16 maturation pattern and aberrant CD56 coexpression, suggesting dysgranulopoiesis. The B-cells (1.7 percent) are polytypic and the T-cells (8.2 percent) show a normal CD4:CD8 ratio with no pan T-cell antigen deletion. Viability is 91.13 percent. The AML panel in the cytogenetics FISH (fluorescence in situ hybridization) study was negative for RUNX1T1/RUNX1 (ETO/AML1), KMT2A (MLL), PML/RARA, CBFB rearrangement, negative for monosomy 5, and deletion of CSF1R/RPS14 on the long arm of chromosome 5 at q33, negative for monosomy 7, and deletion of MDFIC on the long arm of chromosome 7 at q31. The MPN/CML (Chronic myeloid leukemia) panel was also negative for BCR/ABL1 rearrangement, trisomy 8, 9, and deletion of DLEU1, DLEU2 on the long arm of chromosome 13 at q14, and deletion of PTPRT on the long arm of chromosome 20 at q12. Risk stratification based on the Molecular Model classified her as high risk with a score of 3 points and intermediate-risk. Based on the functional status and physical fitness, the patient was deemed to be an intermediate risk but infusion dependent as patient has received multiple platelets and pRBC (Packed red blood cells) transfusions. As a result, the patient was started on Azacitidine therapy, which significantly improved her cell count after two cycles. However, on further follow-up, it was found that patient had progressed to AML (acute myeloid leukemia) and died due to acute respiratory failure secondary to COVID-19 pneumonia. Thus, patient had suspected clinical vaccination failure. It was unknown whether autopsy was performed or not.  The action taken with covid-19 vaccine ad26.cov2.s was not applicable. The outcome of the acute myeloid leukemia (aml), scleroderma, chronic myelomonocytic leukemia (cmml), suspected clinical vaccination failure and sjogren's syndrome was not reported. The authors emphasized the fact that, based on the previous studies reported, the association of scleroderma with CMML is very rare. Also they suspect that the COVID-19 vaccine has triggered and unmasked both the CMML and the associated scleroderma in patient, considering the acute onset and absence of other known triggering factors. The importance of the COVID-19 vaccine is undeniable during this time. This case suggested the possibility of developing CMML associated with limited scleroderma after receiving the J and J COVID vaccine. However, further research needs to be done to confirm the hypothesis and to know the pathogenesis behind the association.  This report was serious (Death, and Other Medically Important Condition). This report was associated with product quality complaint: 90000236774.; Sender's Comments: V0:20220645431- covid-19 vaccine ad26.cov2.s-acute respiratory failure,COVID-19 pneumonia, scleroderma, sjogren's syndrome - The event(s) has an unknown/unclear temporal relationship, is unlabeled, and has unknown scientific plausibility. There is no information on any other factors potentially associated with the event(s). Therefore, this event(s) is considered unassessable.   20220645431- covid-19 vaccine ad26.cov2.s-chronic myelomonocytic leukemia, acute myeloid leukemia - The event(s) shows an incompatible temporal relationship. Therefore, this event(s) is considered not related.( Temporality considered as not suggestive as patient started experiencing events within 4 days; diagnosed as chronic myelomonocytic leukemia  which progressed to acute myeloid leukemia )  20220645431-COVID-19 VACCINE Ad26.COV2.S--suspected clinical vaccination failure . The event(s) has an unknown/unclear temporal relationship, is unlabeled, and has unknown scientific plausibility. There are other factors more likely to be associated with the event(s) than the drug. Specifically: SPECIAL SITUATIONS. Therefore, this event(s) is considered not related.; Reported Cause(s) of Death: COVID-19 PNEUMONIA; ACUTE RESPIRATORY FAILURE