May Chien

All Publications

• Emapalumab Use in Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis in the United States: the REAL-HLH Study. Arthritis & rheumatology (Hoboken, N.J.) Chandrakasan, S., Allen, C. E., Bhatla, D., Carter, J., Chien, M., Cooper, R., Draper, L., Eckstein, O. S., Hanna, R., Hays, J. A., Hermiston, M. L., Hinson, A. P., Hobday, P. M., Isakoff, M. S., Jordan, M. B., Leiding, J. W., Modica, R., Nakano, T. A., Oladapo, A., Patel, S. A., Pednekar, P., Riskalla, M., Sarangi, S. N., Satwani, P., Tandra, A., Walkovich, K. J., Yee, J. D., Zoref-Lorenz, A., Behrens, E. M. 2024

  Abstract

  Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-gamma, approved for treating patients with primary HLH.REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with ≥1 dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH.Fifteen of 105 patients (14.3%) had rheumatologic disease-associated HLH. Of these, 9 (60.0%) had systemic juvenile idiopathic arthritis, and 1 (6.7%) had adult-onset Still's disease. Median (range) age at HLH diagnosis was 5 (0.9-39) years. Most (9/15; 60.0%) patients initiated emapalumab in an intensive care unit. Emapalumab was most frequently initiated for treating refractory or recurrent (10/15; 66.7%) disease. Most patients received HLH-related therapies prior to (10/15; 66.7%) and concurrently (15/15; 100.0%) with emapalumab. Emapalumab-containing regimens stabilized or achieved physician-determined normalization of most laboratory parameters including fibrinogen (11/13; 84.6%), chemokine ligand 9 (7/8; 87.5%), and absolute neutrophil count (6/10; 60%), and reduced glucocorticoid dose by 80%. Overall survival and 12-month survival probability from emapalumab initiation were 86.7%.Emapalumab-containing regimens stabilized or normalized most key laboratory parameters, reduced glucocorticoid dose, and were associated with low disease-related mortality, thereby demonstrating potential benefits in patients with rheumatologic disease-associated HLH.

  View details for DOI 10.1002/art.42985

  View details for PubMedID 39245963

• Drinking Water of Patients With Chronic Kidney Disease-Get the Lead Out. JAMA internal medicine Polasko, A. L., Hsu, C. Y., Chien, M. 2024

  View details for DOI 10.1001/jamainternmed.2024.0901

  View details for PubMedID 38805231

• Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab. Blood advances Chandrakasan, S., Jordan, M. B., Baker, A., Behrens, E. M., Bhatla, D., Chien, M., Eckstein, O. S., Henry, M. M., Hermiston, M. L., Hinson, A., Leiding, J. W., Oladapo, A., Patel, S. A., Pednekar, P., Ray, A., Dávila Saldaña, B. J., Sarangi, S. N., Walkovich, K., Yee, J. D., Zoref-Lorenz, A., Allen, C. E. 2024

  Abstract

  Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-gamma, is approved in the United States to treat primary HLH (pHLH) in patients with refractory, recurrent, progressive disease or intolerance with conventional HLH. REAL-HLH, a retrospective study, conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between November 20, 2018, and October 31, 2021. Forty-six patients met the pHLH classification criteria. Median (range) age at diagnosis was 1.0 (0.3-21.0) year. Emapalumab was initiated for treating refractory (19/46), recurrent (14/46), or progressive (7/46) pHLH. At initiation, 15/46 patients were in the intensive care unit and 35/46 had received prior HLH-related therapies. Emapalumab treatment resulted in normalization of key laboratory parameters, including chemokine ligand 9 (CXCL9) (24/33; 72.7%), ferritin (20/45; 44.4%), fibrinogen (37/38; 97.4%), platelets (39/46; 84.8%), and absolute neutrophil count (40/45; 88.9%). Forty-two (91.3%) patients were considered eligible for transplant. Pre-transplant survival was 38/42 (90.5%). Thirty-one (73.8%) transplant-eligible patients proceeded to transplant and 23/31 (74.2%) of those transplanted were alive at the end of the follow-up period. Twelve-month survival probability from emapalumab initiation for the entire cohort (n=46) was 73.1%. There were no discontinuations due to adverse events. In conclusion, results from the REAL-HLH study, which describes treatment patterns, effectiveness, and outcomes in patients with pHLH treated with emapalumab in real-world settings, are consistent with the emapalumab pivotal phase 2/3 pHLH trial.

  View details for DOI 10.1182/bloodadvances.2023012217

  View details for PubMedID 38429096

• A multidisciplinary approach to unraveling genetic forms of immune dysregulation in children with refractory multilineage cytopenia Gernez, Y., Sathi, B., Camacho, J., Rao, L., Glader, B., Singh, D., Hoyte, E., Lewis, D., Roncarolo, M., Chien, M., Bacchetta, R., Weinacht, K. MOSBY-ELSEVIER. 2024: AB186

  View details for Web of Science ID 001267526000574

• A Single Center Experience for Clinical Evaluation of Paroxysmal Cold Hemoglobinuria and Donath-Landsteiner Testing Villar-Prados, A., Chien, M., Yunce, M., Abdelmonem, M., Duda, M. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-185235

  View details for Web of Science ID 001159900801136

• LENTIVIRAL-MEDIATED GENE THERAPY FOR SEVERE PYRUVATE KINASE DEFICIENCY: RESULTS FROM AN ONGOING GLOBAL PHASE 1 STUDY Lopez Lorenzo, J., Shah, A., Sevilla, J., Navarro, S., Llanos, L., de Camino Gaisse, B., Sanchez, S., Zubicaray, J., Glader, B., Chien, M., Quintana Bustamante, O., Zeini, M., Choi, G., Nicoletti, E., Rao, G., Roncarolo, M., Bueren, J., Schwartz, J., Carlos Segovia, J. SPRINGERNATURE. 2023: 275-276

  View details for Web of Science ID 001110902800354

• A single center experience for clinical evaluation of paroxysmal cold hemoglobinuria and Donath-Landsteiner testing. Transfusion Villar-Prados, A., Abdelmonem, M., Duda, M., Chien, M., Yunce, M. 2023

  Abstract

  Paroxysmal cold hemoglobinuria (PCH) is a rare form of autoimmune hemolytic anemia (AIHA), mainly affecting children. The diagnosis and management are challenging due to similarities to other causes for AIHA and limited availability to Donath-Landsteiner (DL) testing.In this single-center retrospective study, we aimed to characterize the clinical presentation and outcomes of PCH patients, defined as having positive Donath-Landsteiner antibodies, compared to a cohort of AIHA patients.DL-positive patients were observed to have higher lactate dehydrogenase levels and lower reticulocyte counts compared to DL-negative patients, although this was not statistically significant. We also observed that using steroids in DL-positive patients did not significantly impact their recovery.Our findings support the limited published data on PCH patients and further prompt larger multicenter studies to further characterize these patients so that they are more readily identified, especially in centers where DL antibody testing is not readily available.

  View details for DOI 10.1111/trf.17520

  View details for PubMedID 37632701

• LENTIVIRAL-MEDIATED GENE THERAPY FOR SEVERE PYRUVATE KINASE DEFICIENCY: GLOBAL PHASE 1 STUDY RESULTS Shah, A., Lorenzo, J., Sevilla, J., Navarro, S., Llanos, L., Gaisse, B., Sanchez, S., Zubicaray, J., Glader, B., Chien, M., Bustamante, O. Q., Zeini, M., Choi, G., Nicoletti, E., Rao, G., Roncarolo, M., Bueren, J., Schwartz, J., Segovia, J. WILEY. 2023: S133-S134

  View details for Web of Science ID 001042987300264

• Global Phase 1 Study Results of Lentiviral Mediated Gene Therapy for Severe Pyruvate Kinase Deficiency Shah, A. J., Lopez Lorenzo, J., Sevilla, J., Navarro, S., Llanos, L., de Camino Gaisse, B., Sanchez, S., Zubicaray, J., Glader, B., Chien, M., Quintana Bustamante, O., Zeini, M., Choi, G., Nicoletti, E., Rao, G., Roncarolo, M., Bueren, J. A., Schwartz, J., Carlos Segovia, J. CELL PRESS. 2023: 118-119

  View details for Web of Science ID 001045144200219

• Lentiviral-mediated Gene Therapy for Adults and Children with Severe Pyruvate Kinase Deficiency: Results from an Ongoing Global Phase 1 Study Shah, A. J., Lopez Lorenzo, J., Sevilla, J., Navarro, S., Llanos, L., de Camino Gaisse, B., Sanchez, S., Zubicaray, J., Glader, B., Chien, M., Bustamante, O., Zeini, M., Choi, G., Nicoletti, E., Rao, G. R., Grazia Roncarolo, M., Bueren, J. A., Schwartz, J. D., Segovia, J. C. AMER SOC HEMATOLOGY. 2022: 4902-4903

  View details for DOI 10.1182/blood-2022-170948

  View details for Web of Science ID 000893223204404

• The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry. Blood advances MacKenzie, T. C., Schwab, M. E., Lianoglou, B. R., Gano, D., Gonzalez, J., Arvon, R. L., Baschat, A. A., Bianchi, D. W., Bitanga, M., Bourguignon, A., Brown, R. N., Chen, B., Chien, M., Davis-Nelson, S., de Laat, M. W., Ekwattanakit, S., Gollin, Y., Hirata, G., Jelin, A., Jolley, J., Meyer, P., Miller, J., Norton, M. E., Ogasawara, K. K., Panchalee, T., Schindewolf, E., Shaw, S. W., Stumbaugh, T. L., Thompson, A. A., Towner, D., Tsai, P. S., Viprakasit, V., Volanakis, E., Vichinsky, E., Allen, I. E., Zhang, L. 2022

  Abstract

  Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally and 11 were diagnosed postnatally: all 11 spontaneous survivors' genotypes had preserved embryonic zeta globin. We compared three groups of patients; Group 1 were prenatally diagnosed and alive at hospital discharge (n=14), Group 2 were prenatally diagnosed and deceased perinatally (n=5), Group 3 were postnatally diagnosed and alive at hospital discharge (n=11). Group 1 had better outcomes than Groups 2 and 3 in resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation correlated with higher neurodevelopmental (Vineland-3) scores (r= -0.72, P=0.02). Preterm delivery after IUT was seen in 3/16 (19%) of patients who continued their pregnancy. When we combined our data with those from two published series, patients who received ≥2 IUTs had better outcomes than those with 0-1 IUT, including resolution of hydrops, delivery ≥34 weeks' gestation, and 5-minute Apgar scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT versus 5/13 of the 0-1 IUT group (OR 2.74; P=0.01). Thus, fetal transfusions enable survival of patients with ATM with normal neurodevelopment even in patients presenting with hydrops. Non-directive prenatal counseling of expectant parents should include the option of IUTs.

  View details for DOI 10.1182/bloodadvances.2022007823

  View details for PubMedID 36306387

• Longitudinal study of 2 patients with cyclic thrombocytopenia, STAT3, and MPL mutations. Blood advances Zhang, H., Chien, M., Hou, Y., Shomali, W., Brar, R., Ho, C., Han, P., Xu, D., Zhang, B. M., Guo, X., Tolentino, L., Wu, N. C., Tsai, A. G., Jin, J., Witteles, W. H., Chen, Z., Abidi, P., Jangam, D., Krieger, M. S., Craig, M., Bussel, J. B., Gotlib, J. R., Zehnder, J. L. 2022

  Abstract

  Cyclic thrombocytopenia (CTP) is a rare disease of periodic platelet count oscillations. The pathogenesis of CTP remains elusive. To study the underlying pathophysiology and genetic and cellular associations with CTP, we applied systems biology approaches to two patients with stable platelet cycling and reciprocal thrombopoietin (TPO) cycling at multiple time points through 2 cycles. Blood transcriptome analysis revealed cycling of platelet-specific genes, which are in parallel with and precede platelet count oscillation, indicating that cyclical platelet production leads platelet count cycling in both patients. Additionally, neutrophil and erythrocyte-specific genes also showed fluctuations correlating with platelet count changes, consistent with TPO effects on hematopoietic progenitors. Moreover, we found novel genetic associations with CTP. One patient had a novel germline heterozygous loss-of-function (LOF) thrombopoietin receptor (MPL) c.1210G>A mutation, and both had pathogenic somatic gain-of-function (GOF) variants in signal transducer and activator of transcription 3 (STAT3). In addition, both patients had clonal T-cell populations that remained stable throughout platelet count cycles. These mutations and clonal T cells may potentially involve in the pathogenic baseline in these patients rendering exaggerated persistent thrombopoiesis oscillations of their intrinsic rhythm upon homeostatic perturbations. This work provides new insights into the pathophysiology of CTP and possible therapies.

  View details for DOI 10.1182/bloodadvances.2021006701

  View details for PubMedID 35381066

• Therapy-related myeloid neoplasms resembling juvenile myelomonocytic leukemia: a case series and review of the literature. Pediatric blood & cancer Wintering, A., Smith, S., Fuh, B., Rangaswami, A., Dahl, G., Chien, M., Gruber, T. A., Dang, J., Li, L. S., Lenzen, A., Savelli, S., Dvorak, C. C., Agrawal, A. K., Stieglitz, E. 1800: e29499

  Abstract

  Therapy-related myeloid neoplasms (t-MN) are a distinct subgroup of myeloid malignancies with a poor prognosis that include cases of therapy-related myelodysplastic syndrome (t-MDS), therapy-related myeloproliferative neoplasms (t-MPN) and therapy-related acute myeloid leukemia (t-AML). Here, we report a series of patients with clinical features consistent with juvenile myelomonocytic leukemia (JMML), an overlap syndrome of MDS and myeloproliferative neoplasms that developed after treatment for another malignancy.

  View details for DOI 10.1002/pbc.29499

  View details for PubMedID 34939322

• Pediatric acquired factor VIII deficiency presenting as hemarthrosis. Pediatric blood & cancer Daigh, L. H., Chien, M. C., Lo, C. Y. 1800: e29530

  View details for DOI 10.1002/pbc.29530

  View details for PubMedID 34913591

• Lentiviral Mediated Gene Therapy for Pyruvate Kinase Deficiency: Interim Results of a Global Phase 1 Study for Adult and Pediatric Patients Shah, A. J., Lopez Lorenzo, J., Navarro, S., Sevilla, J., Llanos, L., Perez de Camino Gaisse, B., Sanchez, S., Glader, B., Chien, M., Quintana Bustamante, O., Beard, B. C., Law, K. M., Zeini, M., Choi, G., Nicoletti, E., Rao, G. R., Grazia Roncarolo, M., Bueren, J. A., Schwartz, J. D., Segovia, J. C. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-148161

  View details for Web of Science ID 000736398802104

• Lentiviral Mediated Gene Therapy for Pyruvate Kinase Deficiency: Updated Results of a Global Phase 1 Study for Adult and Pediatric Patients Lopez Lorenzo, J., Shah, A. J., Navarro, S., Sevilla, J., Llanos, L., Perez Camino de Gaisse, B., Sanchez, S., Glader, B., Chien, M., Quintana-Bustamante, O., Beard, B. C., Law, K. M., Zeini, M., Choi, G., Nicoletti, E., Rao, G. R., Roncarolo, M., Bueren, J. A., Schwartz, J. D., Segovia, J. C. CELL PRESS. 2021: 42-43

  View details for Web of Science ID 000645188700083

• A challenging case of recurrent idiopathic hemophagocytic lymphohistiocytosis (HLH) initially presenting in an infant with Pneumocystis jirovecii pneumonia Solomon, B., Balagtas, J., Chien, M., Pooni, R., Balboni, I., Weinacht, K., Gernez, Y. SPRINGER/PLENUM PUBLISHERS. 2021: S55

  View details for Web of Science ID 000639851600094

• A Blueprint for Identifying Phenotypes and Drug Targets in Complex Disorders with Empirical Dynamics. Patterns (New York, N.Y.) Krieger, M. S., Moreau, J. M., Zhang, H., Chien, M., Zehnder, J. L., Craig, M. 2020; 1 (9): 100138

  Abstract

  A central challenge in medicine is translating from observational understanding to mechanistic understanding, where some observations are recognized as causes for the others. This can lead not only to new treatments and understanding, but also to recognition of novel phenotypes. Here, we apply a collection of mathematical techniques (empirical dynamics), which infer mechanistic networks in a model-free manner from longitudinal data, to hematopoiesis. Our study consists of three subjects with markers for cyclic thrombocytopenia, in which multiple cells and proteins undergo abnormal oscillations. One subject has atypical markers and may represent a rare phenotype. Our analyses support this contention, and also lend new evidence to a theory for the cause of this disorder. Simulations of an intervention yield encouraging results, even when applied to patient data outside our three subjects. These successes suggest that this blueprint has broader applicability in understanding and treating complex disorders.

  View details for DOI 10.1016/j.patter.2020.100138

  View details for PubMedID 33336196

• Lentiviral Mediated Gene Therapy for Pyruvate Kinase Deficiency: A Global Phase 1 Study for Adult and Pediatric Patients Lorenzo, J., Navarro, S., Shah, A. J., Roncarolo, M., Sevilla, J., Llanos, L., de Gaisse, B., Sanchez, S., Glader, B., Chien, M., Bustamante, O., Beard, B. C., Law, K. M., Zeini, M., Choi, G., Nicoletti, E., Bueren, J. A., Rao, G. R., Schwartz, J. D., Segovia, J. C. AMER SOC HEMATOLOGY. 2020

  View details for DOI 10.1182/blood-2020-137246

  View details for Web of Science ID 000607547204296

• Impact of in utero transfusions in fetuses with hydrops fetalis due to alpha thalassemia Lianoglou, B. R., Gonzalez, V., Velez, J., Norton, M. E., Chen, B., Finley, B., Hirata, G., Ogasawara, K., MacKenzie, T. C., Brown, R. N., Sanchez-Embrey, E., Shaw, S. W., Foe, M., Bitanga, M., Chien, M., Stumbaugh, T., Thompson, A. A., Viprakasit, V., Volanakis, E. J., Vichinsky, E. MOSBY-ELSEVIER. 2020: S300–S301

  View details for DOI 10.1016/j.ajog.2019.11.474

  View details for Web of Science ID 000504997300457

• CLINICAL OUTCOME OF HB KHARTOUM/beta THALASSEMIA COMPOUND HETEROZYGOSITY: A GLIMPSE INTO HOMOZYGOUS HB KHARTOUM Chien, M., Glader, B. WILEY. 2018

  View details for Web of Science ID 000428851200076

• ANTICOAGULATION FOR TREATMENT OF PAIN IN VENOUS MALFORMATIONS Chien, M., Kreimer, S., Teng, J., Marqueling, A., Jeng, M. WILEY. 2018

  View details for Web of Science ID 000428851200243