Severe and fatal anthracycline cardiotoxicity at cumulative doses below 400 mg/m2: Evidence for enhanced toxicity with multiagent chemotherapy

Abstract Background Despite the associated dose-dependent cardiotoxicity, anthracyclines continue to form the backbone of modern chemotherapy regimens. Speckle Tracking Echocardiography (STE) has been a popular method of quantifying cardiac function but most studies have focused on left ventricular function. Research into the effects of anthracyclines on left atrial (LA) and right atrial (RA) function continues to be neglected. Purpose To investigate the effects of doxorubicin, a commonly used anthracycline, on both the LA and RA systolic and diastolic strain and strain-rate parameters in two groups of patients with lymphoma: Group 1 (G1) with a conventional drop in ejection fraction (EF <53%), and Group 2 (G2) without. Methods We retrospectively studied 46 patients treated for lymphoma between 2015 and 2018; G1 (n=12) and G2 (n=34). Echocardiograms performed at baseline (T0), mid-chemotherapy (T1), and post-chemotherapy (T2), were analysed by using offline vendor-independent software (TomTec, 2D Cardiac Performance Analysis). Using 2D STE, LA and RA reservoir, conduit and contractile strains, systolic and diastolic strain-rates were measured. Multi-level longitudinal model was used for statistical analysis.This study was ethically approved by the Health Research Association (REC Reference 18/SS/0139). Results Median age was 64 years (IQR 51–74 years) in G1, and 65 years (IQR 57–73 years) in G2. In G1, there was no significant change in LA reservoir strain with time, however a significant decline with an average mean difference of −7.52 was seen between T0 to T2 (p=0.016) in G2. LA conduit strain did not significantly change in either group with incremental doses of doxorubicin. However, LA contraction strain was seen to significantly increase in G1 between T1 to T2 (p=0.045) with an average change of 7.23. LA peak systolic strain rate, and late diastolic strain rate did not show any significant change with time in both groups. Yet, a significant increase was seen in LA early diastolic strain rate between T0 to T2 (p=0.017) in G1 but not G2. No significant changes were seen in the RA strain parameters in both groups. Conclusion In patient with a reduction in LV function, a significant change was noted in the left atrial contraction strain and early diastolic strain rate with incremental doses of doxorubicin. These changes shows the close relationship between the LA and LV, and the importance of LA in providing a compensatory mechanism for a decline in LV function secondary to anthracycline cardiotoxicity. Funding Acknowledgement Type of funding source: None

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ETMR-15. USE OF HIGH-DOSE CHEMOTHERAPY FOR TWO CHILDREN WITH EMBRYONAL TUMOR WITH MULTILAYERED ROSETTES

Neuro-Oncology ◽

10.1093/neuonc/noaa222.219 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii326-iii326

Author(s):

Shimpei Kusano ◽

Junya Fujimura ◽

Megumi Fujiwara ◽

Akinori Yaguchi ◽

Takeshi Ishibashi ◽

...

Keyword(s):

Local Recurrence ◽

Tumor Resection ◽

Radical Resection ◽

Multicenter Trial ◽

High Dose Chemotherapy ◽

High Dose ◽

Embryonal Tumor ◽

The Central Nervous System ◽

Classification Of Tumors ◽

Multiagent Chemotherapy

Abstract Embryonal tumor with multilayered rosettes (ETMR) is new entity defined in the 4th revised edition of the WHO classification of tumors of the central nervous system. Although radical resection, radiotherapy, and multiagent chemotherapy are considered to be necessary for ETMR, the efficacy of chemotherapy for ETMR in Japan has not been established. Here, we report different clinical courses for two children with localized ETMR treated with the St. Jude medulloblastoma-96 (SJMB96) regimen, which consists of four cycles of high-dose chemotherapy with autologous peripheral blood stem cell transplantation. For both children, the diagnosis of ETMR, C19MC-altered was confirmed after gross total tumor resection. Multiagent chemotherapy was administered following cranio-spinal irradiation with local boost. One month after completion of the treatment, one patient experienced local recurrence but has been in remission for over 2 years after tumor resection and stereotactic irradiation with a CyberKnife and treatment every three weeks with bevacizumab. The other patient also experienced local recurrence after the third cycle of chemotherapy and several times thereafter. Although she again underwent tumor resection and local irradiation, her tumor grew larger and invaded. Because her prognosis was very poor, her parents choose only palliative care. Based on our experience, we believe that continuous chemotherapy at conventional doses is preferred over intensive-dose chemotherapy such as SJMB96. However, the number of reports on chemotherapy for ETMR is still small, and a prospective multicenter trial is needed to establish effective chemotherapy for ETMR.

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Cutaneous Lymphoblastic Lymphoma in Children: Report of Six Cases with Precursor B-cell Lineage

Pediatric and Developmental Pathology ◽

10.1007/s10024-001-0104-4 ◽

2002 ◽

Vol 5 (1) ◽

pp. 45-53 ◽

Cited By ~ 38

Author(s):

Samir B. Kahwash ◽

Stephen J. Qualman

Keyword(s):

Radiation Therapy ◽

T Cell ◽

Subcutaneous Tissue ◽

Bone Marrow Involvement ◽

Distal Tibia ◽

Cell Lineage ◽

Distal Humerus ◽

Bone Lesions ◽

Cutaneous Lesions ◽

Multiagent Chemotherapy

Precursor B lymphoblastic lymphomas (B-LBL) are generally rare, but appear to have a higher incidence in children than in adults. In this report, we describe in detail six cases of B-LBL presenting with cutaneous lesions. Three occurred in the scalp, one in the skin of the thigh, one in the skin of the face and breast, and one in the subcutaneous tissue of the orbit. All six patients are females ranging in age at presentation from 5 to 15 years (mean = 9.6). None of the cases had bone marrow involvement, while two had bone involvement (maxilla, distal tibia, and distal humerus in one case, and distal tibia and orbital bone in another case); only one case had lymphadenopathy (retroperitoneal). Immunohistochemical staining showed positivity for CD79a and CD43 in all six cases. LCA and L26 positivity were also each seen in one case. Staining for MIC-2 (CD99) showed strong positivity in three cases. Vimentin was positive in four cases and TdT was positive in all five patients tested. Staining for keratin, UCHL-1, or CD30 was not encountered. Cases in which cell marker studies by flow cytometry were performed showed positivity for CD10, CD19 with negative CD20, pan-T-cell, and myeloid markers. The five patients who received multiagent chemotherapy are alive with follow-up intervals of 2 to 18 years. Two patients had local recurrences and were given radiation therapy (one with repeating multiagent chemotherapy). One patient (diagnosed in 1962) died of disseminated disease; she had been treated with radiation therapy and 6MP only. Cutaneous B-LBL must be included in the differential diagnosis of small blue cell tumors, especially in children. In contrast to its T-cell counterpart, B-LBL occurs more frequently in females, tends to present as skin or bone lesions, and is associated with a potential cure, even in cases that relapse.

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Targeted expression of cyclin D2 ameliorates late stage anthracycline cardiotoxicity

Cardiovascular Research ◽

10.1093/cvr/cvy273 ◽

2018 ◽

Vol 115 (5) ◽

pp. 960-965 ◽

Cited By ~ 7

Author(s):

Wuqiang Zhu ◽

Sean Reuter ◽

Loren J Field

Keyword(s):

Late Stage ◽

Cyclin D2 ◽

Anthracycline Cardiotoxicity ◽

Targeted Expression

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In vitro modeling of the structure–activity determinants of anthracycline cardiotoxicity

Cell Biology and Toxicology ◽

10.1007/s10565-006-0143-8 ◽

2006 ◽

Vol 23 (1) ◽

pp. 49-62 ◽

Cited By ~ 32

Author(s):

P. Menna ◽

G. Minotti ◽

E. Salvatorelli

Keyword(s):

Anthracycline Cardiotoxicity ◽

In Vitro Modeling ◽

Structure Activity

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Complete Response to Chemotherapy in Intra-Abdominal Desmoplastic Small round Cell Carcinoma. A Case Report

Tumori Journal ◽

10.1177/030089169808400320 ◽

1998 ◽

Vol 84 (3) ◽

pp. 412-416 ◽

Cited By ~ 3

Author(s):

Mario De Lena ◽

Maria Lucia Caruso ◽

Franco Marzullo ◽

Sergio Mancarella ◽

Raffaele Armentano ◽

...

Keyword(s):

Good Health ◽

Complete Response ◽

Complete Disappearance ◽

Round Cell ◽

Small Round Cell ◽

Response To Chemotherapy ◽

Lower Abdominal Quadrant ◽

Antineoplastic Treatment ◽

Multiagent Chemotherapy ◽

The Right

Aims and background The authors report the case of a 23-year-old woman affected by intra-abdominal desmoplastic small round cell tumor (DSRCT) who obtained a complete response to multiagent chemotherapy. DSRCT is a rare, highly aggressive neoplasm generally arising in young people and seldom in females (about 20 cases described in the literature). Methods The patient underwent surgical resection of a large 15 × 15 cm mass located in the right lower abdominal quadrant, but after only 2 months later, two liver metastasis were noted. Thus, she was subjected to an aggressive antineoplastic treatment consisting of three groups of alternating non-cross resistant multiagent regimens administered every 21 days (cis-platin-etoposide-adriamycin-bleomicin; gemcitabine-ifosfamide-dacarbazine; methotrexate-5-fluorouracilfolinic acid) for a total of 9 administrations. Results After one cycle of treatment including the administration of all the three alternated schemes of chemotherapy, a complete disappearance of liver disease was noted. The treatment was relatively well-tolerated and the toxicity was acceptable. At present, after 15 months from diagnosis and 12 months after starting chemotherapy, the patient is disease-free and in good health. Conclusions Even though this study regards only a single patient, it is noteworthy because of the rarity of this neoplasm and because of the infrequent complete responses reported in the literature. The efficacy and manageability of the treatment, suggests that both the timing and schedule used could constitute an important therapeutical option for this aggressive and poorly chemo-responsive tumor.

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LEUKEMIA IN PREGNANCY AND FETAL RESPONSE TO MULTIAGENT CHEMOTHERAPY

Obstetrics and Gynecology ◽

10.1097/00006250-200105000-00039 ◽

2001 ◽

Vol 97 (5) ◽

pp. 809-812

Author(s):

Wendy F. Hansen ◽

Peter Fretz ◽

Stephen K. Hunter ◽

Jerome Yankowitz

Keyword(s):

Multiagent Chemotherapy ◽

Fetal Response ◽

In Pregnancy

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Topical Imiquimod for the Treatment of Relapsed Cutaneous Langerhans Cell Histiocytosis after Chemotherapy in an Elderly Patient

Case Reports in Dermatological Medicine ◽

10.1155/2018/1680871 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Shinsaku Imashuku ◽

Miyako Kobayashi ◽

Yoichi Nishii ◽

Keisuke Nishimura

Keyword(s):

Elderly Patient ◽

Elderly Patients ◽

Diabetes Insipidus ◽

Cytosine Arabinoside ◽

Langerhans Cell Histiocytosis ◽

Langerhans Cell ◽

Central Diabetes Insipidus ◽

Diagnosis And Treatment ◽

Topical Imiquimod ◽

Multiagent Chemotherapy

Diagnosis and treatment of Langerhans cell histiocytosis (LCH) in elderly patients are often difficult. We report here a 61-year-old female suffering from a refractory axillary ulcer for nearly a year, whose biopsy revealed LCH. It was also noted that the patient had other cutaneous papulovesicular eruptions of LCH as well as central diabetes insipidus. The patient was first successfully treated with multiagent chemotherapy (cytosine arabinoside/vinblastine/prednisolone). DDAVP also well controlled diabetes insipidus; however, the axillary ulcer and cutaneous LCH relapsed. Thereafter, we found topical imiquimod to be effective in the treatment of relapsed cutaneous LCH lesions.

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