Fatality owing to pulmonary hemorrhage following pamidronate disodium administration in a neonate with osteogenesis imperfecta type 2: A case report.

We report the case of a patient with osteogenesis imperfecta (OI) who developed pulmonary hemorrhage 4 d after pamidronate disodium (PA) administration, despite a relatively stable respiratory status. Bisphosphonates are introduced to reduce osteoclast activity and are now widely used in patients with OI. Bisphosphonates are typically well-tolerated in children, and the standard of care involves cyclic intravenous administration of PA. However, in practice, there is limited experience with the use of PA for severe OI during the neonatal period, and its safety remains uncertain. This report aimed to describe the respiratory events potentially associated with PA in a neonatal patient with OI type 2, suggesting that serious life-threatening complications of pulmonary hemorrhage may occur after PA administration. Further studies are required to assess the relationship between pulmonary hemorrhage and PA administration, aiming to enhance prophylaxis measures.

Survey of enteral feeding of preterm infants and the human milk bank in Japan.

BACKGROUND: In Japan, the first human milk bank (HMB) was established in 2017, which changed the practice of enteral feeding in neonatal care. This study investigated the practice of enteral feeding of preterm infants after the establishment of the HMB in Japan and examined related future issues. METHODS: A survey on enteral feeding and the use of the HMB was conducted in 251 neonatal intensive care units (NICUs) from December 2020 to February 2021. RESULTS: The response rate was 61%. The ideal times to start enteral feeding for extremely-low-birthweight infants (ELBWI) and very-low-birthweight infants (VLBWI) were within 24 h after birth in approximately 59% and 62% of NICUs, however, only 30% and 46% could do so, respectively. Artificial nutrition was used to initiate enteral feeding for ELBWIs and VLBWIs in in 24% and 56% of NICUs, respectively. Of the NICUs, 92% considered the HMB "necessary" or "rather necessary". Fifty-five percent wanted to use the HMB but could not. The major reasons for this were (1) difficulty in paying the annual membership fee, (2) difficulty obtaining approval from the NICU, and (3) complexity in using the facility. The indications for using and discontinuation of use of donor milk varied among the NICUs. Only in 17%, milk expression was within 1h after delivery. CONCLUSIONS: Compared with before the establishment of the HMB, NICUs are currently more willing to start enteral feeding for preterm infants earlier. However, the implementation of enteral feeding appears to be challenging. Issues related to the HMB highlighted by the responses need to be addressed. Additionally, guidelines for using donor milk should be established.

Mortality and morbidity of extremely low birth weight infants in Japan, 2015.

BACKGROUND: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short-term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. METHODS: We analyzed the mortality, morbidity, and factors related to short-term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. RESULTS: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z-score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. CONCLUSIONS: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long-term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan.

Transfer of Zolpidem to Cord Blood and Breast Milk: A Case Series Evaluating Zolpidem Serum Levels and Outcomes in Birth and Suckling Infants.

Background: Zolpidem is used for insomnia in pregnant and lactating women. Although zolpidem has been shown to cross the placenta and to be secreted into breast milk, it would not be expected to cause any adverse effects in newborn and breastfed infants. However, there is no relevant information on serum zolpidem levels in the newborn and breastfed infant from zolpidem-treated mother. This study aimed to present the outcomes of zolpidem exposure into infant who was delivered or breastfed by a zolpidem-treated mother. Methods: In this case series, zolpidem-treated pregnant women were recruited between September 2019 and April 2022, and maternal serum, cord blood, breast milk, and infants' serum were collected, and the zolpidem concentration in each sample was evaluated. Childbirth outcomes, including 1-month health care checkup, were also evaluated. Results: Three cases were recruited during investigation period. No spontaneous abortion or preterm live deliveries occurred. Oxygen intervention was required in one term infant, but the findings resolved on postpartum day 1. No medical intervention was required in other three infants. Zolpidem was not detected in infants' serum even after breastfeeding. There are no abnormal developmental findings in any of the infants in their 1-month health checkups. Conclusions: Zolpidem transferred into fetal circulation in utero and breast milk, however no harmful findings existed in infants during pregnancy and lactation. Exposure doses through breastfeeding is small, which may be a cause of rare detection from the infants' serum. Due to the limited number of cases, larger studies and integrated review are needed.

Quantitative assessment of coat-hanger ribs detected on three-dimensional ultrasound for prenatal diagnosis of Kagami-Ogata syndrome.

Kagami-Ogata syndrome (KOS14) is a rare disease characterized by omphalocele, polyhydramnios and a bell-shaped thorax. Although the coat-hanger appearance of the ribs on postnatal X-rays is a key diagnostic finding of KOS14, its prenatal diagnosis remains challenging. We encountered a case of KOS14 diagnosed prenatally that showed omphalocele, polyhydramnios, and a bell-shaped narrow thorax. The coat-hanger angle (CHA) measured at the sixth thoracic vertebrae and the ribs using three-dimensional (3D) ultrasonography was 39°, reflecting the coat-hanger appearance of the ribs. Segmental uniparental disomy chromosome 14 (UPD(14)pat) was confirmed by a methylation analysis and microsatellite analysis after birth. The median CHA (minimum, maximum) in 25 normal fetuses was 19 (9, 26) degrees, and a sonographic CHA of 30° may be a border value for diagnosing KOS14. When the combination of omphalocele and polyhydramnios is found prenatally, 3D ultrasonography for CHA might aid in the differential diagnosis of KOS14.

Transfer of brotizolam, periciazine, and sulpiride in cord blood and breast milk, and alprazolam in breast milk: a case report.

BACKGROUND: A high prevalence of mental disorders including depression, anxiety, somatoform, and dissociative disorder is reported during pregnancy, however, information on the transfer of antipsychotics across the placenta and into breast milk is limited. We evaluated brotizolam, periciazine and sulpiride in cord blood, maternal serum, and breast milk, and alprazolam in breast milk. CASE PRESENTATION: A 38-year-old woman with dissociative disorder was treated with brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and alprazolam during lactation. The drug concentration ratios for both cord blood and maternal serum were 33.3 and 61.5% for brotizolam and sulpiride, respectively, and periciazine (metabolite of propericiazine) was not detected in the cord blood. In breast milk, alprazolam (0.9 ng/mL), sulpiride (445.8 ng/mL), and periciazine (0.3 ng/mL) concentrations were noted at 7.5 h after the last dose on postpartum, whereas brotizolam was not detected. The relative infant doses via breast milk were 1.4, 2.7 and 0.02% of the maternal daily dose, respectively. The neonate had no congenital anomalies and did not experience any severe withdrawal symptoms after birth. CONCLUSION: Use of brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and use of alprazolam during lactation were acceptable in this case.

Remdesivir and Human Milk: A Case Study.

INTRODUCTION: Remdesivir was originally developed to treat Ebola hemorrhagic fever, and its efficacy in treating coronavirus disease 2019 was detected during a preliminary analysis of a randomized controlled trial. It is known that Severe Acute Respiratory Syndrome Coronavirus 2 is not transmitted through human milk, but data about the presence of remdesivir in human milk have been lacking. MAIN ISSUE: In this case study, we determined the human milk-to-serum drug concentration ratio and the relative dose of Remdesivir in one participant. MANAGEMENT: The participant, a 28-year-old primipara, was found to have Coronavirus 2 infection in 2019, 2 days after delivery. She was given Remdesivir. The Remdesivir concentration in maternal serum and human milk was measured, and the milk-to-serum drug concentration ratio was found to be low (0.089), as was the relative infant dose (0.0070). The participant could not breastfeed her infant during her Coronavirus 2 infection treatment because in Japan anyone with COVID-19 was completely quarantined. However, she was able to resume breastfeeding after discharge and breastfed her infant for 6 months with supplements. CONCLUSION: Given the low amount of Remdesivir in the participant's milk, the inclusion of antibodies to Severe Acute Respiratory Syndrome Coronavirus 2, which can be expected to protect the infant from infection, and various other benefits of human milk, suggests that breastfeeding is safe during treatment with Remdesivir.

Long-term physical and neurodevelopmental outcomes after antenatal betamethasone administration for congenital heart block prevention.

INTRODUCTION: Congenital heart block (CHB) is associated with a mortality rate of 20% and requires a pacemaker in 70% of cases. Steroids can reduce morbidity and prevent the onset of CHB but may have adverse effects on growth and neurodevelopment. This study aimed to clarify the long-term effects of antenatal betamethasone administration on growth and neurodevelopment. METHODS: The subjects were children with a high risk of CHB due to a high level of maternal anti-SSA/Ro antibody or a maternal history of a previous delivery of a offspring with CHB to whom antenatal betamethasone was administered. Data on body weight, height, and blood pressure were collected as physical outcomes. The Wechsler Intelligence Scale for Children (fourth edition) or the Kyoto Scale of Psychological Development and the Pervasive Developmental Disorders Autism Society Japan Rating Scale was administered to assess the neurodevelopmental outcome. RESULTS: Fourteen children were enrolled. The body weight and height were within normal range in all children. All children had normal intelligence, and none had autism. CONCLUSION: Our study suggested that antenatal betamethasone administration has no negative effects on long-term physical and neurodevelopmental outcomes.

Presence of Hypnotics in the Cord Blood and Breast Milk, with No Adverse Effects in the Infant: A Case Report.

Background: Hypnotics are frequently used for insomnia in pregnant and lactating women. This case study assessed zolpidem concentrations in the cord blood and breast milk and ramelteon concentrations in the breast milk of a woman who was treated with zolpidem and ramelteon for insomnia. Materials and Methods: Zolpidem concentrations were measured in maternal serum, breast milk, and cord blood. Concentrations of ramelteon and M-II, an active ramelteon metabolite, were measured in maternal serum and breast milk. Case Report: A 46-year-old female patient diagnosed with insomnia received 5-10 mg/day zolpidem during pregnancy and lactation and 8 mg/day ramelteon during lactation. A male infant weighing 3,329 g was born at 38 weeks' gestation, with no congenital abnormalities found during pregnancy or at birth. The infant was normal at the 1-month postpartum checkup. The maternal/placental ratio of zolpidem concentrations was 0.1 at 7.4 hours after maternal dosing, similar to that reported in previous studies. The calculated relative infant dose through breast milk based on the maximum drug concentration in breast milk at 2.2 hours after maternal dosing was 2.7% for zolpidem and 0.2% for ramelteon. Ramelteon and its metabolite (M-II) concentrations in the breast milk were equivalent to those in the maternal serum, although the infant exposure of these drugs was low for an oral dose. Conclusions: In the current case, zolpidem transferred into the placenta and breast milk, and ramelteon transferred into the breast milk. Further studies should assess the safety of zolpidem and ramelteon in fetus and breastfed infants.

Long-term neurodevelopmental outcomes of the pump twin in twin reversed arterial perfusion sequence treated by radiofrequency ablation.

OBJECTIVES: To assess long-term neurodevelopmental outcomes in children after radiofrequency ablation (RFA) for twin reversed arterial perfusion (TRAP) sequence. METHODS: This cross-sectional study included children who underwent RFA for the TRAP sequence between 2012 and 2018. We assessed neurodevelopment in children using the Kinder Infant Development Scale, a validated questionnaire. The developmental quotient (DQ) assessed in nine subscales was calculated as the developmental age divided by the chronological age. Neurodevelopmental delay (NDD) was defined as a DQ of <70 points. RESULTS: In total, 38 children from 37 pregnancies underwent RFA for the TRAP sequence during the study period; 6 fetuses died in utero. We sent the questionnaire to the parents of the 32 surviving children and obtained answers for 27 (84%). The median age at the assessment was 2 years and 5 months old. The median total DQ was 111 (80-150). Most median DQs in the nine subscales were above 70. The incidence of NDD was 0% (0/27). There were no marked differences in DQ by chorionicity. CONCLUSIONS: Children who survived after RFA for TRAP sequence showed favorable long-term neurodevelopmental outcomes. Radiofrequency ablation seems to rarely affect fetal neurodevelopment. Pregnant women with TRAP sequence are encouraged to be treated by RFA.

Risk Profiling of the Solomon Technique versus Selective Technique of Fetoscopic Laser Surgery for Twin-Twin Transfusion Syndrome.

We evaluated the outcomes and adverse events after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) using the Solomon technique in comparison to the selective technique. A retrospective analysis of a single-center consecutive cohort of FLS-treated TTTS using the selective (January 2010 to July 2014) and Solomon (August 2014 to December 2017) techniques was performed. Among 395 cases, 227 underwent selective coagulation and 168 underwent the Solomon technique. The incidence rates of recurrent TTTS (Solomon vs. selective: 0% vs. .9%, p = .510) and twin anemia-polycythemia sequence (.6% vs. .4%, p = .670) were very low in both groups. The incidence rates of placental abruption (Solomon vs. selective: 10.7% vs. 3.5%, p = .007) and preterm premature rupture of the membranes (pPROM) with subsequent delivery before 32 weeks (20.2% vs. 7.1%, p < .001) were higher in the Solomon group. The median birth recipient weight was significantly smaller in the Solomon group (1790 g vs. 1933 g, p = .049). The rate of survival of at least one twin was significantly higher in the Solomon group (98.2% vs. 93.8%, p = .046). The Solomon technique and total laser energy were significant risk factors for pPROM (odds ratio: 2.64, 1.07, 95% CI [1.32, 5.28], [1.01, 1.13], p = .006, p = .014, respectively). These findings suggest that the Solomon technique led to superior survival outcomes but increased risks of placental abruption, pPROM and fetal growth impairment. Total laser energy was associated with the occurrence of pPROM. Close attention to adverse events is required for perinatal management after FLS to treat TTTS using the Solomon technique.

Neonatal systemic juvenile Xanthogranuloma with Hydrops diagnosed by Purpura skin biopsy: a case report and literature review.

BACKGROUND: Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult. CASE PRESENTATION: A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition. CONCLUSIONS: This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.

The Japanese experience and pharmacokinetics of antenatal maternal high-dose immunoglobulin treatment as a prophylaxis for neonatal hemochromatosis in siblings.

Background: Neonatal hemochromatosis (NH) is a rare but serious disease causing fulminant hepatic failure. The recurrence rate of NH in a subsequent infant of a mother with an affected infant is 70-90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) treatment has been reported to be effective for preventing NH recurrence. However, data on the IgG concentrations during this treatment are limited.Objective: We report a Japanese experience and present a pharmacokinetic simulation model of IgG during IVIG treatment.Methods: Women with histories of pregnancy diagnosed with NH were treated with IVIG weekly from the second trimester until the end of gestation. Serum IgG levels during treatment were collected frequently and pharmacokinetics were simulated by a two-compartment model.Results: Six women were included during eight pregnancies. None experienced severe adverse events. Three out of eight infants showed temporary liver dysfunction, but none required any treatment. A simulation study showed that the estimated trough and peak levels of IgG concentrations during IVIG were 2000-3000 and 4000-5000 mg/dl, respectively.Conclusion: This treatment prevented the recurrence of NH in siblings in Japanese women. We examined the details of serum IgG concentrations and introduced a new pharmacokinetic simulation model of IgG concentrations during IVIG treatment.

Effects of Domperidone in Increasing Milk Production in Mothers with Insufficient Lactation for Infants in the Neonatal Intensive Care Unit.

Breast milk is the optimum for all infants, but hospitalization in the neonatal intensive care unit can cause separation of mothers and infants, which often interferes with milk secretion. Some reports show that domperidone is effective in promoting milk secretion. However, the Food and Drug Administration in the United States cautioned to not use domperidone for increasing milk volume because domperidone carries some risk of cardiac events, including QT prolongation, cardiac arrest, and sudden death. In contrast, it is used in Canada, Australia, and the United Kingdom with safety. The pharmacodynamics and pharmacokinetics of drugs may vary by race or ethnic origin, and it is not known whether domperidone is effective or safe for Japanese. In this study we report the effects of domperidone for Japanese mothers with insufficient lactation. Ten mothers were enrolled in a pilot study. After confirming that there were no abnormal findings on the electrocardiogram, the mothers were administered domperidone. Seven of 10 who took domperidone increased their milking volume. Prolactin was increased in 9 of 10 mothers. Adverse events were observed in two mothers, one headache and one abdominal pain; all symptoms were mild and improved promptly; and there were no adverse cardiac events. These results are consistent with reports from other countries. Domperidone may tentatively be considered effective for increasing milk secretion in Japanese mothers as in other populations. Our preliminary study of 10 cases indicates the need for further studies with larger sample sizes to assess the efficacy and safety of domperidone.

Effect and Complications of Everolimus Use for Giant Cardiac Rhabdomyomas with Neonatal Tuberous Sclerosis.

Most cardiac rhabdomyomas with tuberous sclerosis (TS) are asymptomatic and spontaneously regress. However, some cases require surgical intervention due to arrhythmia and severe obstruction of cardiac inflow or outflow. We report herein a neonatal case of giant cardiac rhabdomyomas with TS and insufficient pulmonary blood flow from the right ventricle. Lipoprostaglandin E1 was necessary to maintain patency of the ductus arteriosus. We used everolimus, a mammalian target of rapamycin inhibitor, to diminish the cardiac rhabdomyomas. After treatment, the rhabdomyomas shrank rapidly, but the serum concentration of everolimus increased sharply (maximum serum trough level: 76.1 ng/mL) and induced complications including pulmonary hemorrhage, liver dysfunction, and acne. After the everolimus level decreased, the complications resolved. Everolimus may be a viable treatment option for rhabdomyomas, but its concentration requires close monitoring to circumvent complications associated with its use.

Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in AML and MDS.

This study was performed to assess the utility of tumor-derived fragmentary DNA, or circulating tumor DNA (ctDNA), for identifying high-risk patients for relapse of acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloSCT). We retrospectively collected tumor and available matched serum samples at diagnosis and 1 and 3 months post-alloSCT from 53 patients with AML/MDS. After identifying driver mutations in 51 patients using next-generation sequencing, we designed at least 1 personalized digital polymerase chain reaction assay per case. Diagnostic ctDNA and matched tumor DNA exhibited excellent correlations with variant allele frequencies. Sixteen patients relapsed after a median of 7 months post-alloSCT. Both mutation persistence (MP) in bone marrow (BM) at 1 and 3 months post-alloSCT and corresponding ctDNA persistence (CP) in the matched serum (MP1 and MP3; CP1 and CP3, respectively) were comparably associated with higher 3-year cumulative incidence of relapse (CIR) rates (MP1 vs non-MP1, 72.9% vs 13.8% [P = .0012]; CP1 vs non-CP1, 65.6% vs 9.0% [P = .0002]; MP3 vs non-MP3, 80% vs 11.6% [P = .0002]; CP3 vs non-CP3, 71.4% vs 8.4% [P < .0001]). We subsequently evaluated whether subset analysis of patients with 3 genes associated with clonal hematopoiesis, DNMT3A, TET2, and ASXL1 (DTA), could also be helpful in relapse prediction. As a result, CP based on DTA gene mutations also had the prognostic effect on CIR. These results, for the first time, support the utility of ctDNA as a noninvasive prognostic biomarker in patients with AML/MDS undergoing alloSCT.

MYRF haploinsufficiency causes 46,XY and 46,XX disorders of sex development: bioinformatics consideration.

Disorders of sex development (DSDs) are defined as congenital conditions in which chromosomal, gonadal or anatomical sex is atypical. In many DSD cases, genetic causes remain to be elucidated. Here, we performed a case-control exome sequencing study comparing gene-based burdens of rare damaging variants between 26 DSD cases and 2625 controls. We found exome-wide significant enrichment of rare heterozygous truncating variants in the MYRF gene encoding myelin regulatory factor, a transcription factor essential for oligodendrocyte development. All three variants occurred de novo. We identified an additional 46,XY DSD case of a de novo damaging missense variant in an independent cohort. The clinical symptoms included hypoplasia of Müllerian derivatives and ovaries in 46,XX DSD patients, defective development of Sertoli and Leydig cells in 46,XY DSD patients and congenital diaphragmatic hernia in one 46,XY DSD patient. As all of these cells and tissues are or partly consist of coelomic epithelium (CE)-derived cells (CEDC) and CEDC developed from CE via proliferaiton and migration, MYRF might be related to these processes. Consistent with this hypothesis, single-cell RNA sequencing of foetal gonads revealed high expression of MYRF in CE and CEDC. Reanalysis of public chromatin immunoprecipitation sequencing data for rat Myrf showed that genes regulating proliferation and migration were enriched among putative target genes of Myrf. These results suggested that MYRF is a novel causative gene of 46,XY and 46,XX DSD and MYRF is a transcription factor regulating CD and/or CEDC proliferation and migration, which is essential for development of multiple organs.

Low Levels of Amlodipine in Breast Milk and Plasma.

OBJECTIVE: Few clinical reports have addressed the use of the antihypertensive drug amlodipine during breastfeeding. The objective of this study is to characterize concentration-time profiles of amlodipine in maternal and infant plasma, and milk. MATERIALS AND METHODS: Plasma and breast milk samples were obtained from eight nursing mothers and their nine newborn nursing infants (median postnatal age: 6.5 days, range 5-7 days). Participants were recruited from February 2009 to June 2009. Multiple blood and milk samples were obtained from the mothers over a 24 hours dosing interval. The blood of infants was also obtained at before and 8 hours after nursing. Amlodipine concentrations were determined by high-performance liquid chromatography. Relative infant dose (RID) was calculated by dividing the infant's dose via milk in mg/kg/day by the maternal dose in mg/kg/day, assuming that a daily intake of milk is 150 mL/kg/day in the infants. RESULTS: Maximal amlodipine concentrations in mothers ranged from 4.4 to 14.7 ng/mL in plasma, and 6.5 to 19.7 ng/mL in milk (Average milk/plasma ratio: 1.4). RID was 3.4% of the maternal weight-adjusted dose. All plasma concentrations in infants were under the quantitation limit (0.4 ng/mL). CONCLUSION: Infant exposure to amlodipine in breast milk appears very small, suggesting that amlodipine can be used with little influence on infants during breastfeeding.

Circulating tumor DNA dynamically predicts response and/or relapse in patients with hematological malignancies.

A growing body of evidence suggests that tumor-derived fragmentary DNA, known as circulating tumor DNA (ctDNA), has the potential to serve as a non-invasive biomarker for disease monitoring. However, in the setting of hematological malignancy, few published studies support the utility of ctDNA. We retrospectively investigated ctDNA levels of 17 patients with various hematological malignancies who had achieved remission after first-line therapy. We identified somatic driver mutations by next-generation sequencing, and designed droplet digital PCR assays for each mutation to measure ctDNA. Variant allele frequencies of ctDNA changed in association with clinical response in all patients. Eight patients clinically relapsed after a median of 297 days post-first-line therapy (termed, "relapsed group"); the remaining nine patients remained disease-free for a median of 332 days (termed, "remission group"). Among patients in the relapsed group, ctDNA levels increased more than twofold at paired serial time points. In marked contrast, ctDNA levels of all patients in the remission group remained undetectable or stable during clinical remission. Notably, ctDNA-based molecular relapse demonstrated a median 30-day lead time over clinical relapse. In summary, ctDNA monitoring may help identify hematologic cancer patients at risk for relapse in advance of established clinical parameters.