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False-positive restaging PET scans involving the spleen in two patients with aggressive non-Hodgkin lymphoma.

We report 2 patients with aggressive non-Hodgkin lymphoma who had positive restaging PET scans limited to the spleen and no significant uptake in nodal areas of previously known disease. Examination of the resected spleens from both patients revealed extensive inflammation surrounding necrotic tumor with no evidence of viable lymphoma or active infection. It is suggested that close observation of such patients for evidence of progressive disease may be considered as opposed to immediate intervention.

The status of high-dose chemotherapy with hematopoietic stem cell transplantation in germ cell tumor patients.

BACKGROUND AND OBJECTIVES: Germ cell tumors (GCTs) are very chemosensitive cancers, in which high-dose chemotherapy (HDCT) has been investigated as salvage therapy or as first-line treatment in poor prognosis patients. This paper presents an update of available information in order to define the status of HDCT in GCT patients. INFORMATION SOURCES: The authors have been working in this field, contributing to international clinical trials and to peer-reviewed journals with original papers. The material examined in this review includes articles published in journals covered by MedLine, reviews f

Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.

INTRODUCTION: Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expre

Hepatoblastoma presenting with focal nodular hyperplasia after treatment of neuroblastoma.

Focal nodular hyperplasia (FNH) is a benign, poorly understood hepatic tumor that is rare in children. Although there is no evidence for malignant degeneration, FNH can occur adjacent to a malignancy. Here, the case of a 4-year-old boy with a hepatic mass and history of stage IV neuroblastoma is presented. Initial imaging and core-needle biopsy were consistent with FNH. However, after left lateral segmentectomy, pathologic examination revealed a malignant tumor most consistent with small cell undifferentiated hepatoblastoma as well as 3 foci of FNH in the surrounding parenchyma.

Impact of oncogene rearrangement patterns on outcomes in patients with double-hit non-Hodgkin lymphoma.

BACKGROUND: Double-hit lymphomas (DHLs) are collectively defined as B-cell non-Hodgkin lymphomas harboring rearrangements of MYC as well as B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6). To the authors' knowledge, the impact of specific oncogene rearrangements on outcomes of patients with DHL who are treated with immunochemotherapy has not been previously described. METHODS: The authors identified patients whose diagnostic tissue specimens underwent metaphase karyotyping or fluorescence in situ hybridization for MYC as well as both BCL2 and BCL6 rearrangements. Cohorts were defined

High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overa

Outcome prediction by molecular detection of minimal residual disease in bone marrow for advanced neuroblastoma.

BACKGROUND: We have determined whether sequential molecular detection of minimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma (NB). PROCEDURE: Bone marrow samples from 19 patients over 12 months of age with stage 4 neuroblastoma were sequentially examined for tumor cell contamination by detecting tyrosine hydroxylase (TH) mRNA using reverse transcription-polymerase chain reaction (RT-PCR). All patients received repetitive multi-drug chemotherapy including cisplatin, cyclophosphamide or ifosphamide, adriamycin, and etoposide or vi

Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life: a selective review of intergroup rhabdomyosarcoma study group experience and rationale for Intergroup Rhabdomyosarcoma Study V.

PURPOSE: To review the importance of prognostic factors in developing new protocols for children with rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Four studies conducted by the Intergroup Rhabdomyosarcoma Study (IRS) Group from 1972 through 1991. RESULTS: Favorable prognostic factors are: (1) undetectable distant metastases at diagnosis; (2) primary sites in the orbit and nonparameningeal head/neck and genitourinary nonbladder/prostate regions; (3) grossly complete surgical removal of localized tumor at the time of diagnosis; (4) embryonal/botryoid histology; (5) tumor size < or = 5 cm; and

The severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis.

Mononuclear cells (MNCs) containing peripheral blood stem cells (PBSCs) were obtained from solid-tumor patients undergoing mobilizing chemotherapy followed by granulocyte colony-stimulating factor for PBSC transplantation-supported dose-intensified anticancer chemotherapy and were transplanted into unconditioned "nonleaky" young severe combined immunodeficient mice. Multilineage engraftment was shown by flow cytometry and immunocytochemistry using monoclonal antibodies to various human cell surface antigens as well as identification of human immunoglobulin in murine sera. Within a dose range o

A syndrome of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia/malignancy associated with t(8;13)(p11;q11): description of a distinctive clinicopathologic entity.

We report two patients with a distinctive biphenotypic hematologic disorder characterized by lymphoblastic lymphoma (LBL), eosinophilia, and myeloid malignancy and/or hyperplasia associated with a t(8;13)(p11;q11) chromosomal translocation in both bone marrow and lymph node specimens. Both patients presented with lymphadenopathy pathologically classified as LBL with a T-cell immunophenotype, myeloid hyperplasia of the bone marrow, and peripheral blood eosinophilia. The first patient achieved clinical complete remission after receiving several regimens of chemotherapy and remains disease-free 1

Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts.

Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell

[Efficacy of 1 384 cases of peritoneal carcinomatosis underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy].

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum … us docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, whil …

Aldoxorubicin: a tumor-targeted doxorubicin conjugate for relapsed or refractory soft tissue sarcomas.

Despite available therapies after initial systemic therapy, prognosis remains poor in relapsed or refractory soft tissue sarcomas (STS). The rational and clinical development of novel agents to improve outcomes in this area of high unmet need is desperately warranted. Aldoxorubicin is a prodrug of doxorubicin that binds to serum albumin immediately after administration through an acid-sensitive hydrazone linker and is subsequently transported to tumor tissues where the acidic environment cleaves the linker and facilitates delivery of a tumor-targeted drug payload. In clinical studies to date,

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… pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), and malignant peripheral nerve sheath tumors (MPNSTs), anthracycline (eg, doxorubicin)-based systemic therapy remains the standard first-line therapy. 1 Dose-intensive combination chemotherapy with doxorubicin and ifosfamide … In the relapsed or refractory setting, the efficacy of aldoxorubicin was directly compared with standard therapies including dacarbazine, doxorubicin, pazopanib, ifosfamide, and gemcitabine/docetaxel in patients with previously treated advanced STS. …

Successful Treatment with High-Dose Chemotherapy Followed by Autologous Stem-Cell Transplantation in a Patient with Metastatic Germ Cell Tumor.

Although testicular germ cell tumors (GCTs) are known to curable disease even in cases with metastatic disease, patients in intermediate or poor-risk group may experience disease progression or refractory to the initial chemotherapy and needed second-line therapy. Long-term disease-free survival was unsatisfactory in relapsed/refractory patients with poor-risk factors and clinical trials for those patients are still insufficient. High-dose chemotherapy (HDCT) with stem-cell rescue may be an effective alternative for conventional chemotherapy-resistant patients who are eligible for transplantat

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… Most patients will generally receive 4 cycles of Vinblastine/ifosfamide/cisplatin or paclitaxel/ifosfamide/cisplatin as a salvage regimen [ 5 , 6 ]. However, long-term disease-free survival was unsatisfactory in relapsed/refractory patients with poor-risk factors. … Table 1 Contemporaneous laboratory investigations AFP, α-fetoprotein; auto-SCT, autologous stem-cell transplantation; β-hCG, beta-human chorionic gonad-otropin; LDH, lactate dehydrogenase; TIP, paclitaxel/ifosfamide/cisplatin; VIP, etoposide, ifosfamide, and cisplatin combination. …

Spinal epidural extraskeletal Ewing sarcoma in an adolescent boy: a case report.

Extraskeletal Ewing sarcoma (EES) represents a rare soft tissue malignant neoplasm histologically similar to skeletal Ewing sarcoma. It occurs mainly in adolescents and young adults and commonly affects the paravertebral regions. The differential diagnosis includes other small, blue round cells tumors. The authors report a case of an EES involving the spinal epidural and paravertebral spaces in an adolescent boy. EES diagnosis was confirmed by features of histologic analysis and immunohistochemistry and by the presence of the t(11;22)(q24;q12) chromosomal translocation by reverse transcriptase

Altered expression of resistance associated genes in hepatoblastoma xenografts incorporated into mice following treatment with adriamycin or cisplatin.

To study the development of drug resistance in childhood hepatoblastoma (HB) using a model closely related to in vivo conditions, we cultivated HB xenografts from 3 patients into mice and treated these tumors with either adriamycin (ADR) or cisplatin (CIS). Determination of the relative expression levels of various resistance associated genes by a cDNA-PCR approach showed: a) Significantly enhanced MDR1 gene expression levels after treatment with ADR in each case. b) Significantly enhanced glutathione S-transferase mu (GST mu) gene expression levels after treatment with CIS in 2/3 xenografts.

Molecular Mechanisms and Biomarkers Associated with Chemotherapy-Induced AKI.

Acute kidney injury (AKI) is a life-threatening condition characterized by a rapid and transient decrease in kidney function. AKI is part of an array of conditions collectively defined as acute kidney diseases (AKD). In AKD, persistent kidney damage and dysfunction lead to chronic kidney disease (CKD) over time. A variety of insults can trigger AKI; however, chemotherapy-associated nephrotoxicity is increasingly recognized as a significant side effect of chemotherapy. New biomarkers are urgently needed to identify patients at high risk of developing chemotherapy-associated nephrotoxicity and s

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… Another commonly used nephrotoxic agent is ifosfamide, an alkylating agent. Its nephrotoxicity is particularly relevant considering that it is mostly observed in pediatric patients [ 74 , 75 ]. Thirty percent of the children treated with ifosfamide will consequently develop CKD [ 76 ]. … Clinically, AKI associated with ifosfamide is characterized by tubular dysfunction [ 75 ]. In fact, ifosfamide mainly affects the S3 segment of the proximal tubule and/or the distal nephron resulting in Fanconi syndrome. …

Analysis of 2023 World Health Organization cancer Essential Medicines List and concordance with resource-stratified guidelines.

BackgroundThe World Health Organization (WHO) Essential Medicines List (EML) and resource-stratified guidelines both prioritize high-value medicines. We compared the 2023 EML cancer medicines list with global cancer statistics, examined the proportion of EML therapies recommended by resource-stratified guidelines, and identified gaps that merit evaluation by the WHO EML Committee.MethodsWe compared the 2023 EML medicines for adult cancers with cancer incidence and mortality data from GLOBOCAN 2022. We cross-referenced the EML with 2 resource-stratified guidelines (National Comprehensive Cancer

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… | | | | Methotrexate | | | | Mesna | | | | Ewing sarcoma ( n = 7) | Cyclophosphamide | | | | Dactinomycin | | | | Doxorubicin | | | | Etoposide | | | | Ifosfamide | | | | Vincristine | | | | Mesna | | | | Gastrointestinal stromal tumor ( n = 1) | Imatinib | | … | | | Etoposide | | | | Ifosfamide | | | | Paclitaxel | | | | Vinblastine | | | | Mesna | | | | Testicular germ cell tumor ( n = 7) | Bleomycin | | | | Carboplatin | | | | Cisplatin | | | | Etoposide | | | | Ifosfamide | | | | Vinblastine | | | | Mesna | …

A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab.

Hepatosplenic gamma-delta T-cell lymphoma is a rare, usually fatal lymphoma and available literature on management is sparse. Allografting is probably the only curative option. We describe a further case with a dramatic, though transient response to Fludarabine and Alemtuzumab combination, following a failure of conventional chemotherapy. Given the dreadful prognosis with conventional chemotherapy, it is a regimen worth pursuing as a disease reduction strategy prior to allograft where appropriate.