Palo Alto, CA 94304
Fax: (650) 497-8959
University of Southern California Keck School of Medicine, Los Angeles, CA, 05/14/2010
LAC+USC Internal Medicine and Pediatric Residency, Los Angeles, CA, 06/30/2014
Stanford University Hematology and Oncology Fellowship, Palo Alto, CA, 06/30/2020
Stanford University Pediatric Hematology Oncology Fellowship, Palo Alto, CA, 06/30/2020
Hematology, American Board of Internal Medicine
Internal Medicine, American Board of Internal Medicine
Pediatric Hematology-Oncology, American Board of Pediatrics
Pediatrics, American Board of Pediatrics
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
View details for Web of Science ID 001042987300264
View details for Web of Science ID 001045144200219
View details for DOI 10.1182/blood-2022-170948
View details for Web of Science ID 000893223204404
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
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 (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
View details for DOI 10.1002/pbc.29530
View details for PubMedID 34913591
View details for DOI 10.1182/blood-2021-148161
View details for Web of Science ID 000736398802104
View details for Web of Science ID 000645188700083
View details for Web of Science ID 000639851600094
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
View details for DOI 10.1182/blood-2020-137246
View details for Web of Science ID 000607547204296
View details for DOI 10.1016/j.ajog.2019.11.474
View details for Web of Science ID 000504997300457
View details for Web of Science ID 000428851200076
View details for Web of Science ID 000428851200243