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Cancer Jul 2009The role of myeloablative chemotherapy in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors (MB/ST-PNET) is controversial, in...
High-dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors: the impact of prior radiotherapy on outcome.
BACKGROUND
The role of myeloablative chemotherapy in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors (MB/ST-PNET) is controversial, in particular in patients who develop recurrent disease after craniospinal radiotherapy.
METHODS
In this retrospective analysis, the authors investigated the outcome of children with recurrent MB/ST-PNET who were referred for myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue at Childrens Hospital Los Angeles.
RESULTS
Thirty-three children were referred for myeloablative chemotherapy: Fourteen of those children were never transplanted because of pre-transplant adverse events, and 19, including 6 without and 13 with previous irradiation, underwent transplant. Conditioning regimens included a backbone of thiotepa, which was given either in a single cycle or in multiple sequential cycles. The 3-year post-transplant event-free survival rate in unirradiated versus previously irradiated children was 83% +/- 15% versus 20% +/- 12%, respectively (P = .04). One child who had never been exposed to radiotherapy died of toxicity; the other children received post-transplant radiotherapy and remained disease free. Nine previously irradiated children experienced 4 toxic deaths and 6 tumor recurrences (1 patient had both): An interval of <1 year between initial radiotherapy and myeloablative chemotherapy predicted a greater risk of toxic death (P = .02), whereas a history of meningeal metastases at diagnosis and a poor response to the initial rescue therapy predicted a greater risk of post-transplant recurrence (P = .03 and P = .08, respectively).
CONCLUSIONS
Myeloablative doses of thiotepa-based chemotherapy and radiotherapy were able to cure most children who had radiotherapy-naive, chemoresponsive recurrences. Children who developed recurrences after craniospinal radiotherapy had poorer outcomes; however, cure was possible in those who had good prognostic features at presentation, chemoresponsive recurrences, and a long interval between initial radiotherapy and myeloablative chemotherapy.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Combined Modality Therapy; Cranial Irradiation; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Medulloblastoma; Neoplasm Recurrence, Local; Neuroectodermal Tumors, Primitive; Supratentorial Neoplasms; Survival Rate; Thiotepa
PubMed: 19402050
DOI: 10.1002/cncr.24341 -
Experimental Hematology Jan 2022Chemotherapy-induced bone marrow (BM) injury is a significant cause of morbidity and mortality in acute myeloid leukemia (AML). Time to hematologic recovery after...
Chemotherapy-induced bone marrow (BM) injury is a significant cause of morbidity and mortality in acute myeloid leukemia (AML). Time to hematologic recovery after standard ("7 + 3") myeloablative chemotherapy can vary considerably among patients, but the factors that drive or predict BM recovery remain incompletely understood. Here, we assessed the composition of innate and adaptive immune subsets in the regenerating BM (day 17) after induction chemotherapy and related it to hematologic recovery in AML. T cells, and in particular the CD4 central memory (CD4CM) T-cell subset, were significantly enriched in the BM after chemotherapy, suggesting the relative chemoresistance of cells providing long-term memory for systemic pathogens. In contrast, B cells and other hematopoietic subsets were depleted. Higher frequencies of the CD4CM T-cell subset were associated with delayed hematopoietic recovery, whereas a high frequency of natural killer (NK) cells was related to faster recovery of neutrophil counts. The NK/CD4CM ratio in the BM after chemotherapy was significantly associated with the time to subsequent neutrophil recovery (Spearman's ρ = -0.723, p < 0.001, false discovery rate <0.01). The data provide novel insights into adaptive immune cell recovery after injury and identify the NK/CD4CM index as a putative predictor of hematopoietic recovery in AML.
Topics: Adaptive Immunity; Adult; Aged; Antineoplastic Agents; CD4-Positive T-Lymphocytes; Cells, Cultured; Female; Humans; Immunity, Innate; Killer Cells, Natural; Leukemia, Myeloid, Acute; Male; Middle Aged; Young Adult
PubMed: 34800603
DOI: 10.1016/j.exphem.2021.11.003 -
Deutsches Arzteblatt International Jun 2018Primary central nervous system lymphoma is a diffuse large B-celllymphoma with exclusive manifestation in the central nervous system (CNS), leptomeninges, and eyes. Its...
BACKGROUND
Primary central nervous system lymphoma is a diffuse large B-celllymphoma with exclusive manifestation in the central nervous system (CNS), leptomeninges, and eyes. Its incidence is 0.5 per 100 000 persons per year.Currently, no evidence-based standard of care exists.
METHODS
This review is based on pertinent publications (2000-2017) retrieved by aselective search in PubMed.
RESULTS
The clinical and neuroradiological presentation of primary CNS lymphoma isoften nonspecific, and histopathological confirmation is obligatory. The disease, if left un- treated, leads to death within weeks or months. If the patient's general condition permits, treatment should consist of a high-dose chemotherapy based on methotrexate (HD- MTX) combined with rituximab and other cytostatic drugs that penetrate the blood-brain barrier. Long-term survival can be achieved in patients under age 70 by adding non- myeloablative consolidation chemotherapy or high-dose chemotherapy with autologous stem cell transplantation (HD-AST) to the induction therapy. Clinical trials comparing the efficacy and toxicity of these two treatment strategies are currently underway. Con- solidation whole-brain radiotherapy is associated with the risk of severe neurotoxicity and should be reserved for patients who do not qualify for systemic treatment. Some 30% of patients are refractory to primary treatment, and at least 50% relapse. In patients who are still in good general condition, relapse can be managed with HD-AST. Re- exposure to conventional HD-MTX-based polychemotherapy is another option, if the initial response was durable. The 5-year survival rate of all treated patients is 31%,according to registry data.
CONCLUSION
Current recommendations for the treatment of primary CNS lymphomaare based on only a small number of prospective clinical trials. Patients with this disease should be treated by interdisciplinary teams in experienced centers, andpreferably as part of a controlled trial.
Topics: Adult; Aged; Central Nervous System Diseases; Combined Modality Therapy; Drug Therapy; Female; Germany; Humans; Lymphoma; Male; Methotrexate; Middle Aged; Prognosis; Rituximab
PubMed: 29999484
DOI: 10.3238/arztebl.2018.0419 -
Systematic Reviews Nov 2015The objective of the study is to conduct a systematic review to compare the effects of high-dose chemotherapy (HDCT) with autologous haematopoietic stem cell... (Meta-Analysis)
Meta-Analysis
The role of high-dose myeloablative chemotherapy with haematopoietic stem cell transplantation (HSCT) in children with central nervous system (CNS) tumours: protocol for a systematic review and meta-analysis.
OBJECTIVES
The objective of the study is to conduct a systematic review to compare the effects of high-dose chemotherapy (HDCT) with autologous haematopoietic stem cell transplantation (HSCT) versus standard-dose chemotherapy (SDCT) in children with malignant central nervous system (CNS) tumours.
METHODS
Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Ten electronic databases will be searched, along with citation searching and reference checking. Studies assessing the effects of HDCT with HSCT in children with CNS tumours will be included. The outcomes are survival (overall, progression-free, event-free, disease-free), response rates, short- and long-term adverse events and health-related quality of life (HRQoL). Two reviewers will independently screen and select randomised and non-randomised controlled trials and controlled and uncontrolled observational studies for inclusion. Quality assessment will be tailored to the different study designs. Where possible data will be summarised using combined estimates of effect for the hazard ratio for survival outcomes and the risk ratio for response rates. A fixed effect model will be used; sub-group analyses and meta-regression will be used to explore potential sources of heterogeneity between studies.
DISCUSSION
Given the poor prognosis of malignant brain tumours in children in terms of survival and quality of life, this review will help guide clinical practice by summarising the current evidence on the use of high-dose myeloblative chemotherapy with stem cell support in children with CNS tumours.
Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Clinical Protocols; Disease-Free Survival; Dose-Response Relationship, Drug; Hematopoietic Stem Cell Transplantation; Humans; Infant; Neoplasm Recurrence, Local; Nervous System Neoplasms; Prognosis; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Young Adult
PubMed: 26589619
DOI: 10.1186/s13643-015-0155-7 -
British Journal of Haematology Nov 1997Previous studies have suggested that non-transferrin-bound plasma iron (NTBI) is present in patients undergoing cytotoxic chemotherapy, and that this may exacerbate...
Previous studies have suggested that non-transferrin-bound plasma iron (NTBI) is present in patients undergoing cytotoxic chemotherapy, and that this may exacerbate untoward organ damage and increase the risk of bacterial infections following chemotherapy. However, the source of NTBI during myelosuppressive chemotherapy is controversial. In this study we have examined the kinetics of the appearance and disappearance of NTBI with chemotherapy. NTBI was present in only two out of 24 patients prior to chemotherapy but, following chemotherapy, was present in 19 patients, with peak NTBI levels at 5 d after onset of chemotherapy (mean 3.06 microM). Thereafter levels fell, but were still detectable in seven patients 14 d after the end of chemotherapy. The appearance of NTBI was associated with a sudden rise in transferrin saturation, but NTBI was detected on four occasions in the absence of full transferrin saturation. We have also established that daunorubicin cannot itself liberate NTBI from serum. There was no relationship between induced NTBI levels and serum iron or ferritin levels, previous or current blood transfusions, disease stage, or the type of chemotherapy given. The appearance of NTBI following chemotherapy was inverserely related to the fall in reticulocytes and serum transferrin receptor (TfR) levels, suggesting that NTBI formation is a consequence of suspension of erythropoietic activity.
Topics: Adolescent; Adult; Blood Transfusion; Daunorubicin; Female; Hematopoiesis; Hodgkin Disease; Humans; Iron; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Myeloablative Agonists; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Transferrin; Transferrin; Transplantation Conditioning
PubMed: 9375751
DOI: 10.1046/j.1365-2141.1997.4143221.x -
Medecine Sciences : M/S Dec 2009The first treatment ever by radio-immunotherapy (RIT) was performed by William H. Beierwaltes in 1951 and was a success. Fifty years later, the main question is to find... (Review)
Review
The first treatment ever by radio-immunotherapy (RIT) was performed by William H. Beierwaltes in 1951 and was a success. Fifty years later, the main question is to find ways of extending the success of radiolabelled anti-CD20 antibodies in indolent non-Hodgkin's lymphoma to other forms of cancer. Solid tumours are much more radioresistant than lymphomas, but they respond to RIT if the lesions are small. Clinical situations of residual or minimal disease are thus the most likely to benefit from RIT in the adjuvant or consolidation settings. For disseminated disease, like leukemias or myelomas, the problem is different: beta- particles emitted by the radioactive atoms classically used for cancer treatment (iodine-131 or yttrium-90) disperse their energy in large volumes (ranges 1 mm to 1 cm) and are not very effective against isolated cells. Advances in RIT progress in two directions. One is the development of pretargeting strategies in which the antibody is not labelled but used to provide binding sites to small molecular weight radioactivity vectors (biotin, haptens). These techniques have been shown to increase tumour to non-target uptake ratios and anti-tumour efficacy has been demonstrated in the clinic. The other approach is the use of radionuclides adapted to the various clinical situations. Lutetium-177 or copper-67, because of the lower energy of their emission, their relatively long half-life and good gamma emission, may significantly improve RIT efficacy and acceptability. Beyond that, radionuclides emitting particles such as alpha particles or Auger electrons, much more efficient to kill isolated tumour cells, are being tested for RIT in the clinic. Finally, RIT should be integrated with other cancer treatment approaches in multimodality protocols. Thus RIT, now a mature technology, should enter a phase of well designed and focused clinical developments that may be expected to afford significant therapeutic advances.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Biotinylation; Combined Modality Therapy; Drug Administration Schedule; Drug Delivery Systems; Haptens; Hematologic Neoplasms; Humans; Immunoconjugates; Immunoglobulin G; Models, Molecular; Myeloablative Agonists; Neoplasms; Protein Conformation; Radioimmunodetection; Radioimmunotherapy; Tissue Distribution
PubMed: 20035676
DOI: 10.1051/medsci/200925121039 -
Journal of Dental Research Feb 2015Various chemotherapeutic agents used in patients with hematopoietic malignancy cause serious side effects, including myelosuppression and immunosuppression.... (Comparative Study)
Comparative Study
Various chemotherapeutic agents used in patients with hematopoietic malignancy cause serious side effects, including myelosuppression and immunosuppression. Immunosuppression makes patients more susceptible to infection, resulting in an increased risk of infectious complications, including the development of severe septicemia that may be life-threatening. It is necessary for dental staff to be familiar with an appropriate protocol in such cases and to share information about the chemotherapy with a hematologist. To verify the effectiveness of our dental intervention protocol, we conducted a prospective study on the incidence of complications for each myelosuppressive grade of chemotherapy in patients with hematopoietic malignancy. We compared the incidence of complications between treatment P (patients who finished all the dental treatments according to the protocol) and treatment Q (patients who did not) per grade (A, B, C, D) and incidence of systemic or oral findings. We also compared the incidence of oral complication related to the residual teeth between first chemo (patients who were undergoing chemotherapy for the first time) and prior chemo (not the first time). There were significant differences in inflammatory complications between treatment P and treatment Q. We found that both systemic and oral inflammatory complications increased with higher-grade myelosuppressive chemotherapy. Additionally, there was a significant difference between the incidence of oral complications related to the residual teeth between first chemo and prior chemo. Complete implementation of the dental intervention protocol was associated with fewer oral and systemic infectious and inflammatory complications in patients with hematopoietic malignancies undergoing chemotherapy. The incidence of oral and systemic complications also increased with grade of chemotherapy. These results support the validity of our dental intervention protocol. We should pay close attention to the oral state of de novo hematopoietic malignancy patients.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Marrow; Clinical Protocols; Dental Care for Chronically Ill; Dental Caries; Dental Prosthesis; Female; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Myeloablative Agonists; Oral Hygiene; Periodontal Diseases; Prospective Studies; Tooth Extraction; Young Adult
PubMed: 25503612
DOI: 10.1177/0022034514561768 -
International Journal of Cell Cloning Jan 1990The results of in vivo studies conducted with colony-stimulating factors (CSFs) in autologous bone marrow transplantation (ABMT) are summarized. Our own data obtained... (Review)
Review
The results of in vivo studies conducted with colony-stimulating factors (CSFs) in autologous bone marrow transplantation (ABMT) are summarized. Our own data obtained from in vitro models dealing with the use and possible applications of CSFs in ABMT are reported. In particular, we show data concerning: 1) the use of interleukin 3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 1 to expand hematopoietic progenitor cell growth in the early phase of ABMT; 2) in vitro marrow purging with Mafosfamide and GM-CSF in chronic myelogenous leukemia; and 3) growth requirements of MY10-derived leukemic colony-forming units. The use of CSFs, alone or in combination, may provide us with new strategic approaches for the treatment of acute and chronic leukemias. CSFs in combination with chemotherapeutic agents are very promising agents for purging marrow prior to ABMT.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Colony-Stimulating Factors; Cyclophosphamide; Hematopoiesis; Humans; In Vitro Techniques; Leukemia, Myeloid; Neutropenia; Transplantation, Autologous
PubMed: 2182739
DOI: 10.1002/stem.5530080725 -
Immunology and Allergy Clinics of North... May 2010The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by a triad of diagnostic clinical elements: immunodeficiency, eczema, and hemorrhage caused by... (Review)
Review
The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by a triad of diagnostic clinical elements: immunodeficiency, eczema, and hemorrhage caused by thrombocytopenia with small-sized platelets. The formal proof that hematopoietic cell transplantation (HCT) could be used to cure WAS revealed a requirement for both immunosuppression and myelosuppression that still underlies the standard approach to curative therapy today. The current short- and long-term toxicities of HCT are the main stumbling block for the ability to cure every patient with WAS and X-linked thrombocytopenia, and much remains to be done.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; CD40 Antigens; Chemotherapy, Adjuvant; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Immunity, Cellular; Myeloablative Agonists; Rituximab; Stem Cell Niche; Wiskott-Aldrich Syndrome
PubMed: 20493395
DOI: 10.1016/j.iac.2010.02.001 -
Transplantation and Cellular Therapy Jan 2021Autologous hematopoietic cell transplantation (AHCT) is a standard of care for several subtypes of high-risk lymphoma, but durable remissions are not achieved in the...
Autologous hematopoietic cell transplantation (AHCT) is a standard of care for several subtypes of high-risk lymphoma, but durable remissions are not achieved in the majority of patients. Intensified conditioning using CD45-targeted antibody-radionuclide conjugate (ARC) preceding AHCT may improve outcomes in lymphoma by permitting the delivery of curative doses of radiation to disease sites while minimizing toxicity. We performed sequential phase I trials of escalating doses of yttrium-90 (Y)-labeled anti-CD45 antibody with or without BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy followed by AHCT in adults with relapsed/refractory or high-risk B cell non-Hodgkin lymphoma (NHL), T cell NHL (T-NHL), or Hodgkin lymphoma (HL). Twenty-one patients were enrolled (16 NHL, 4 HL, 1 T-NHL). Nineteen patients received BEAM concurrently. No dose-limiting toxicities were observed; therefore, the maximum tolerated dose is estimated to be ≥34 Gy to the liver. Nonhematologic toxicities and engraftment kinetics were similar to standard myeloablative AHCT. Late myeloid malignancies and 100-day nonrelapse deaths were not observed. At a median follow-up of 5 years, the estimates of progression-free and overall survival of 19 patients were 37% and 68%, respectively. Two patients did not receive BEAM; one had stable disease and the other progressive disease post-transplant. The combination of Y-anti-CD45 with BEAM and AHCT was feasible and tolerable in patients with relapsed and refractory lymphoma. The use of anti-CD45 ARC as an adjunct to hematopoietic cell transplantation regimens or in combination with novel therapies/immunotherapies should be further explored based on these and other data.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy; Lymphoma; Neoplasm Recurrence, Local; Yttrium Radioisotopes
PubMed: 32980545
DOI: 10.1016/j.bbmt.2020.09.021