Clinical Focus


  • Classical Hematology
  • Hematology
  • Hemoglobinopathy
  • Pediatric Hematology-Oncology
  • Bleeding Disorders
  • Anemia, Sickle Cell
  • Thalassemia

Academic Appointments


Professional Education


  • Board Certification: American Board of Pediatrics, Pediatric Hematology-Oncology (2021)
  • Medical Education: University of Southern California Keck School of Medicine (2010) CA
  • Fellowship: Stanford University Pediatric Hematology Oncology Fellowship (2020) CA
  • Fellowship: Stanford University Hematology and Oncology Fellowship (2020) CA
  • Board Certification: American Board of Internal Medicine, Hematology (2019)
  • Board Certification: American Board of Pediatrics, Pediatrics (2014)
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2014)
  • Residency: LACplusUSC Internal Medicine and Pediatric Residency (2014) CA

Clinical Trials


  • Emicizumab for Severe Von Willebrand Disease (VWD) and VWD/Hemophilia A Recruiting

    Von Willebrand Disease (VWD) is the most common inherited bleeding disorder affecting up to 0.1% of the population, is usually characterized by mucocutaneous bleeding, HMB, surgical bleeding or other hemostatic challenges. Severe bleeding events require VWF concentrates administered solely through intravenous access. Emicizumab (Hemlibra) is a monoclonal bispecific antibody developed to bind activated FIX and FX and mimic FVIII cofactor functionality. Hemlibra is administered via subcutaneous injection rather than intravenous infusion. The hypothesis of this study is that Emicizumab is safe and efficacious for prophylaxis in severe VWD and concomitant VWD/hemophilia patients.

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  • A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT) Not Recruiting

    The primary purpose of this study is to compare the effect of mitapivat versus placebo on anemia in participants with alpha- or beta-non-transfusion dependent thalassemia (NTDT).

    Stanford is currently not accepting patients for this trial.

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  • A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) Not Recruiting

    The primary purpose of this study is to compare the effect of mitapivat versus placebo on transfusion burden in participants with transfusion-dependent alpha- or beta-thalassemia (TDT).

    Stanford is currently not accepting patients for this trial.

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2023-24 Courses


All Publications


  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • CLINICAL OUTCOME OF HB KHARTOUM/beta THALASSEMIA COMPOUND HETEROZYGOSITY: A GLIMPSE INTO HOMOZYGOUS HB KHARTOUM Chien, M., Glader, B. WILEY. 2018
  • ANTICOAGULATION FOR TREATMENT OF PAIN IN VENOUS MALFORMATIONS Chien, M., Kreimer, S., Teng, J., Marqueling, A., Jeng, M. WILEY. 2018