OBJECTIVE: To investigate the efficacy, prognosis and safety of decitabine combined with modified EIAG regimen in the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). METHODS: The clinical data of 44 patients with relapsed/refractory AML and high-risk MDS admitted to our hospital from January 2017 to December 2020 were analyzed retrospectively. The patients were equally divided into D-EIAG group (decitabine combined with EIAG regimen) and D-CAG group (decitabine combined with CAG regimen) according to clinical treatment regimen. The complete response (CR), CR with incomplete hematologic recover (CRi), morphologic leukemia-free state (MLFS), partial response (PR), overall response rate (ORR), modified composite complete response (mCRc), overall survival (OS) time, 1-year OS rate, myelosuppression and adverse reactions between the two groups were compared. RESULTS: In D-EIAG group, 16 patients (72.7%) achieved mCRc (CR+CRi+MLFS), 3 patients (13.6%) achieved PR, and ORR (mCRc+PR) was 86.4%. In D-CAG group, 9 patients (40.9%) achieved mCRc, 6 patients (27.3%) achieved PR, and ORR was 68.2%. Difference was observed in mCRc rate between the two groups (P=0.035), but not in ORR (P>0.05). The median OS time of D-EIAG group and D-CAG group was 20 (2-38) months and 16 (3-32) months, and 1-year OS rate was 72.7% and 59.1%, respectively. There was no significant difference in 1-year OS rate between the two groups (P>0.05). After induction chemotherapy, the median time for absolute neutrophil count recovery to 0.5×10⁹/L in D-EIAG group and D-CAG group was 14 (10-27) d and 12 (10-26) d, for platelet count recovery to 20×10⁹/L was 15 (11-28) d and 14 (11-24)d, the median red blood cell suspension transfusion volume was 8 (6-12) U and 6 (6-12) U, and the median apheresis platelet transfusion volume was 4 (2-8) U and 3 (2-6) U, respectively. There were no statistically significant differences in comparison of the above indicators between the two groups (P>0.05). The hematological adverse reactions of patients were mainly myelosuppression. Grade III-IV hematological adverse events occurred in both groups (100%), with no increase in the incidence of non-hematological toxicities such as gastrointestinal reactions or liver function damage. CONCLUSION Decitabine combined with EIAG regimen in the treatment of relapsed/refractory AML and high-risk MDS can improve remission rate, provide an opportunity for subsequent therapies, and have no increase in adverse reactions compared with D-CAG regimen.
Humans ; Decitabine/therapeutic use* ; Treatment Outcome ; Retrospective Studies ; Cytarabine ; Myelodysplastic Syndromes/drug therapy* ; Leukemia, Myeloid, Acute/drug therapy* ; Bone Marrow Diseases/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVE: To investigate the effect of course delay of CCLG-ALL-2008 regimen on the relapse of paediatric B-cell acute lymphoblastic leukemia (B-ALL) patients. METHODS: Paediatric B-ALL patients newly diagnosed and treated with CCLG-ALL-2008 regimen in the Children's Hospital of Soochow University from January 2011 to December 2014 were retrospectively analyzed to clarify the relationship between chemotherapy course delay and relapse, and explore the causes of course delay which led to relapse. Patients were followed up until July 2019. RESULTS: The correlation between treatment delay (number of weeks) and relapse rate was statistically significant (P=0.034), and hazard ratio indicated that longer than 4 weeks had a significant effect. The effect of positive minimal residual disease (MRD) (1×10^-4≤MRD≤1×10^-2) at the 12th week on the relapse rate was also statistically significant (P=0.041). Among the causes of treatment delay, the effect of myelosuppression on the relapse rate was statistically significant (P=0.01). CONCLUSION Treatment delay exceeding 4 weeks, positive MRD at the 12th week, and myelosuppression are independent prognostic factors for relapse.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bone Marrow Diseases/drug therapy* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Humans ; Neoplasm, Residual/drug therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Recurrence ; Retrospective Studies ; Treatment Outcome

Hepatic osteodystrophy is frequent complication in patients with chronic liver disease, particularly with chronic cholestasis. We report a male infant with congenital hepatoblastoma, who had osteodystrophy complicated by multiple bone fractures despite adequate supplementation of fat-soluble vitamins including vitamin D. He was born by Caesarean section because of a 7 cm–sized abdominal mass detected by prenatal ultrasonography. The pathologic diagnosis was hepatoblastoma, PRETEXT staging III or IV. Whole body bone scan at the time of diagnosis showed no abnormal uptake. Oral vitamin D3 of 2,000 IU/day was administered with other fat-soluble vitamins. Serum direct bilirubin level gradually increased up to 28.9 mg/dL at postnatal 6 days and was above 5 mg/dL until 110 days of age. Bony changes consistent with rickets became apparent in left proximal humerus since 48 days of age, and multiple bone fractures developed thereafter. With resolving cholestasis by chemotherapy, his bony lesions improved gradually after add-on treatment of bisphosphonate and parenteral administration of vitamin D with calcium. High level of suspicion and prevention of osteodystrophy is needed in patients with hepatoblastoma, especially when cholestasis persists.
Bilirubin ; Calcium ; Cesarean Section ; Cholecalciferol ; Cholestasis ; Diagnosis ; Drug Therapy ; Female ; Fractures, Bone ; Hepatoblastoma ; Humans ; Humerus ; Infant ; Liver Diseases ; Male ; Pregnancy ; Rickets ; Ultrasonography, Prenatal ; Vitamin D ; Vitamins

Osteoporosis is a major, growing healthcare issue. This is especially of concern in an ageing population like that of Singapore. Osteoporotic patients are at risk of fractures, which can result in increased morbidity and mortality. The use of antiresorptive therapy with bisphosphonates or denosumab has been proven to reduce fracture risk. However, the use of these medications has rarely been associated with the development of osteonecrosis of the jaw, a potentially debilitating condition affecting one or both jaws. Appropriate understanding of the patient's antiresorptive therapy regime, as well as early institution of preventive dental measures, can play an important role in preventing medication-related osteonecrosis of the jaw (MRONJ). Regular monitoring and prompt referral to specialist care is warranted for patients with established MRONJ.
Aged ; Bone Density Conservation Agents ; adverse effects ; therapeutic use ; Denosumab ; adverse effects ; therapeutic use ; Diphosphonates ; adverse effects ; therapeutic use ; Humans ; Jaw Diseases ; chemically induced ; prevention & control ; Osteonecrosis ; chemically induced ; prevention & control ; Osteoporosis ; complications ; drug therapy ; Osteoporotic Fractures ; complications ; drug therapy ; Risk Factors ; Singapore ; Treatment Outcome

Bone is a common metastatic site of cancer. Bone metastasis reduces life expectancy and results in serious symptoms and complications such as bone pain, pathological fractures, and spinal cord compression, decreasing quality of life by restricting sleep and mobility. Treatment for bone metastasis includes drugs (pure analgesics, hormones, cytotoxic chemotherapy, and bisphosphonates, among others), external radiation therapy, surgery, and radionuclide therapy using bone-targeting radiopharmaceuticals. Particulate radiation with α- or β-rays is used as a bone-targeting radiopharmaceutical in radionuclide therapy. β-Emitters have lower energy and a longer range than α-emitters and have less tumoricidal activity and deliver more radiation to adjacent normal tissue. Therefore, the main therapeutic effect of bone-targeting β-emitters such as ⁸⁹Sr-dichloride is bone pain palliation rather than enhanced survival. In contrast, α-emitters such as ²²³Ra-dichloride have high energy and a short range, resulting in greater tumoricidal activity and less radiation damage to adjacent normal tissue. Treatment with bone-targeting α-emitters can improve survival and decrease bone pain. This review focuses on the principles and clinical utility of several clinically available bone-targeting radiopharmaceuticals in metastatic bone disease.
Analgesics ; Bone Diseases ; Diphosphonates ; Drug Therapy ; Fractures, Spontaneous ; Life Expectancy ; Neoplasm Metastasis ; Quality of Life ; Radiopharmaceuticals ; Spinal Cord Compression

OBJECTIVE: Spondylitis is often chemotherapy resistant and requires long-term treatment. Without adequate chemotherapy, the outcome can be fatal or result in severe neurologic damage. Therefore, differentiating the etiology of spondylitis is very important, particularly in spontaneous cases. As the prevalence of tuberculosis in Korea has decreased in recent years, updated clinical research about spondylitis is warranted.METHODS: From April 2010 to March 2016, data from spondylitis patients were collected retrospectively. In total, 69 patients (51 with pyogenic spondylitis and 18 with tuberculous spondylitis) were included. Clinical data, laboratory findings including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, measurements of Cobb angles at the initial and final follow-up, and radiologic features on magnetic resonance imaging (MRI) scans were evaluated. To test differences between the pyogenic and tuberculous groups, numerical data were compared using the student’s t-test and Mann-Whitney U test, and categorical data were compared using the chi-square test and Fisher’s exact test.RESULTS: The patients’ mean age was 60.0 years. Male sex was slightly predominant (56.5%). There was no difference in mean age and sex between the two groups. The pyogenic group had a relatively higher proportion of immunocompromised patients. The peak CRP value was higher in the pyogenic group than in the tuberculous group (14.08 mg/dL and 8.50 mg/dL, respectively, p=0.009), whereas the ESR was not significantly different between the groups (81.5 mm/h and 75.6 mm/h, respectively, p=0.442). Radiologically, the presence of disc space sparing and vertebral body collapse differed between the groups. In the tuberculous group, the disc was more commonly preserved on contrast-enhanced MRI (50% and 23.5%, respectively, p=0.044), and vertebral body collapse was more common (66.6% and 15.7%, respectively, p < 0.001). The mean length of hospitalization was longer in the pyogenic group (56.5 days and 41.2 days, respectively, p=0.001). Four mortality cases were observed only in the pyogenic group. The most commonly isolated microorganism in the pyogenic group was Staphylococcus aureus (S. aureus) (methicillin susceptible S. aureus and methicillin resistant S. aureus [MRSA] in 8 and 4 cases, respectively).CONCLUSION: The clinical and radiological manifestations of spontaneous spondylitis differ based on the causative organism. Pyogenic spondylitis patients tend to have a higher CRP level and a more severe clinical course, whereas tuberculous spondylitis patients present with destruction of the vertebral body with disc sparing more frequently. The presence of MRSA is increasing in community-acquired spondylitis cases.
Bacterial Infections ; Blood Sedimentation ; Bone Diseases, Infectious ; C-Reactive Protein ; Discitis ; Drug Therapy ; Follow-Up Studies ; Hospitalization ; Humans ; Immunocompromised Host ; Korea ; Magnetic Resonance Imaging ; Male ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Mortality ; Osteomyelitis ; Prevalence ; Retrospective Studies ; Spondylitis ; Staphylococcus aureus ; Tuberculosis

BACKGROUND: The aim of this study was to evaluate the effects of darbepoetin alfa (DA) on hemoglobin (Hb) concentration and the need for transfusions in multiple myeloma (MM) patients receiving chemotherapy with novel agents. METHODS: Of 251 patients with MM who received DA therapy for at least 4 weeks, 142 who did not receive RBC transfusion during 4 weeks after DA initiation and started DA therapy at baseline Hb <10.0 g/dL were analyzed. RESULTS: After 4 weeks of DA therapy, 80 (60.6%) of 132 patients with evaluable data had Hb that increased ≥1.0 g/dL from baseline, while 50 (37.9%) had Hb that increased ≥2.0 g/dL from baseline. Pretreatment Hb level did not correlate with the proportion of patients with increased Hb. The median duration of DA therapy was 9.0 weeks. At the end of DA therapy, of 135 patients with evaluable data, 86 (60.6%) had Hb that increased ≥1.0 g/dL from baseline, while 67 (47.2%) had Hb that increased ≥2.0 g/dL from baseline. Stage III disease according to the International Staging System and absence of myeloma bone disease at diagnosis were independent predictors of higher Hb response during early DA therapy. CONCLUSION: We demonstrated the efficacy of DA therapy in a homogeneous group of MM patients receiving chemotherapy. DA therapy significantly increased Hb concentration, regardless of baseline Hb level.
Anemia ; Bone Diseases ; Darbepoetin alfa* ; Diagnosis ; Drug Therapy* ; Erythropoietin ; Humans ; Multiple Myeloma*

The prevention and treatment of fragility fractures is evolving continuously. Adequate fracture care should involve treating the fracture itself as well as the underlying bone disease. Although effective treatments of osteoporosis are available, a large proportion of patients with fragility fractures are not prescribed anti-osteoporotic medications after their injury. Recent advances in diagnostic tools and medications allow for a more effective and comprehensive treatment of fragility fractures.
Accidental Falls ; Bone Diseases ; Drug Therapy ; Humans ; Osteoporosis

BACKGROUND/AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that typically presents in the form of skin manifestations with or without lymph node and bone marrow involvement. Given its rarity and recent recognition as a distinct pathological entity, no standard of treatment exists for this aggressive disease and its prognosis is particularly dismal. METHODS: We retrospectively analyzed clinical features and treatment outcomes of patients who were diagnosed with BPDCN between 2000 and 2014. RESULTS: Ten patients had a median age at diagnosis of 41 years (range, 18 to 79), and seven patients were male. Sites of disease involvement were the skin (n = 7), lymph node (n = 5), bone marrow (n = 2), liver (n = 2), spleen (n = 2), and soft tissue (n = 1). Intensified chemotherapy regimens such as hyperCVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine), and VPDL (vincristine, methylprednisolone, daunorubicin, L-asparaginase) were used as a first-line treatment. Although all patients treated with intensified chemotherapy showed an objective response (five patients with complete response) with median progression-free survival of 11.2 months (range 6.2 to 19.4), complete remission was not sustained for more than 2 years in any case. The response was relatively long-lived compared with previously reported CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, but the above regimens do not result in long-term remission. CONCLUSIONS: All patients treated with hyperCVAD or VPDL showed an objective response, but the duration of response was relatively short. Thus, the development of more effective induction as well as consolidation treatment strategy should be warranted to improve this rare disease entity.
Bone Marrow ; Cyclophosphamide ; Daunorubicin ; Dendritic Cells* ; Dexamethasone ; Diagnosis ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Hematologic Neoplasms ; Humans ; Korea* ; Liver ; Lymph Nodes ; Male ; Methotrexate ; Methylprednisolone ; Prognosis ; Rare Diseases ; Retrospective Studies ; Skin ; Skin Manifestations ; Spleen ; Vincristine

No abstract available.
Bone Diseases, Developmental/diagnosis/drug therapy/*genetics ; Child ; Fibrillin-1/*genetics ; Hand/diagnostic imaging ; Heterozygote ; Human Growth Hormone/therapeutic use ; Humans ; Limb Deformities, Congenital/diagnosis/drug therapy/*genetics ; Male ; Pelvis/diagnostic imaging