Prognostic Value of Immunocytologic Detection of Bone Marrow Metastases in Neuroblastoma

Moss, Thomas J.; Reynolds, C. Patrick; Sather, Harland N.; Romansky, Stephen G.; Hammond, G. Denman; Seeger, R C

doi:10.1056/nejm199101243240403

Cited by 218 publications

(121 citation statements)

References 39 publications

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“…Following Island, NY, USA) supplemented with 15% fetal bovine completion of induction therapy, three patients were serum (GIBCO) at a cell volume of 6.0 × 10 6 cells/ml as determined to be in a complete response (CR), five had a described. 19 The cell suspension was incubated at room very good partial response (VGPR), and three had a partial temperature for 45 min with a cocktail of antibodies generresponse (PR) ( Table 1). All 11 received myeloablative chemotherapy followed by PBSC rescue (Table 4).…”

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confidence: 99%

“…No patient developed hypocalcemia or citalkaline phosphatase staining as described. 19 Positive conrate toxicity. However, one patient did become hypotensive trol slides were prepared with cells from the neuroblastoma during the pheresis, and required fluid administration.…”

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confidence: 99%

“…The fourth patient relapsed in her bone marrow 15 months following analyzed samples of peripheral blood and bone marrow from seven patients sequentially during therapy using sensi-PBSC rescue, and was not further evaluated to determine if there were additional sites of recurrent disease per the tive immunocytologic methods to determine if tumor cells were present. 18,19 Although NB cells from individual request of his family. Post-relapse, two patients received no further therapy.…”

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Treatment of poor-risk neuroblastoma patients with high-dose chemotherapy and autologous peripheral stem cell rescue

Cohn

Moss²,

Hoover

et al. 1997

Bone Marrow Transplant

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Summary:than 20% have long-term survival. 1,2 Because chemotherapy dose-intensity has been shown to correlate strongly with response and progression-free survival in metastatic A single institutional pilot study was conducted in which 12 poor-risk neuroblastoma (NB) patients were uni-NB, 3 many centers are currently treating poor-risk patients with consolidation regimens that include myeloablative formly treated with multi-agent induction chemotherapy followed by myeloablative consolidation chemochemotherapy or chemoradiotherapy followed by allogeneic bone marrow transplant (BMT) or autologous BMT. therapy and unpurged peripheral blood stem cell (PBSC) rescue. In addition to using standard criteria While the efficacy of myeloablative vs nonmyeloablative consolidation therapy has not been determined, some of the for evaluating response to induction chemotherapy, tumor cell contamination of the peripheral blood and/or best long-term survival rates have been reported with highdose myeloablative chemotherapy with or without totalbone marrow was analyzed in seven patients by immunocytology using a panel of five anti-NB monobody irradiation, and bone marrow rescue. 2,4-8 However, the ability to provide bone marrow stem cells for patient clonal antibodies. Seven patients had morphologic evidence of bone marrow disease at the time of diagnosis, rescue following intensive therapy can be limited by marrow contamination with tumor cells, and by the lack of and two additional patients had tumor cells detected in bone marrow samples by immunocytology prior to the adequate marrow reserves to harvest sufficient numbers of stem cells. second cycle of chemotherapy. After three cycles of chemotherapy, two of the 12 patients continued to haveRescue with peripheral blood stem cells (PBSCs) has several advantages over autologous bone marrow. The proevidence of bone marrow disease. Samples from 29 PBSC harvests collected from nine patients were also genitor cell collection can be performed on an outpatient basis without general anesthesia, and in general PBSCs can analyzed for the presence of contaminating tumor cells by immunocytology. In each case, the stem cells were be successfully harvested in patients who do not have adequate marrow reserves. 9 In addition, rescue with PBSCs found to be free of tumor. Eleven of the 12 patients underwent myeloablative therapy and PBSC rescue; results in a significantly reduced cytopenic period after myeloablative therapy. [9][10][11] Further, studies in adults have five patients remain alive without disease progression, 28+ to 53+ months from diagnosis, and six patients have indicated that the peripheral blood is enriched with stem cells during the recovery phase following chemotherapy, developed recurrent disease. We conclude that PBSCs can be successfully harvested from children with NB, and with proper timing and growth factor support, higher yields of stem cells can be obtained from peripheral stem and used for hematopoietic reconstitution following myeloablative chemotherapy. However, more ...

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confidence: 99%

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Treatment of poor-risk neuroblastoma patients with high-dose chemotherapy and autologous peripheral stem cell rescue

Cohn

Moss²,

Hoover

et al. 1997

Bone Marrow Transplant

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“…nosis (Jauch et al 1996;Pantel et al 1993a;Lindemann et al 1992;Moss et al 1991;Berger et al 1988) and demonstration of dynamic postoperative development after curative tumor resection of CK18-positive cells in bone marrow being associated with later clinical outcome (Heiss et al 1995a) suggest the biological relevance of these cells with clinical implications.…”

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confidence: 99%

Immunocytochemical Phenotyping of Disseminated Tumor Cells in Bone Marrow by uPA Receptor and CK18: Investigation of Sensitivity and Specificity of an Immunogold/Alkaline Phosphatase Double Staining Protocol

Allgayer

Heiss

Riesenberg

et al. 1997

J Histochem Cytochem.

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SUMMARYPhenotyping of cytokeratin (CK)18-positive cells in bone marrow is gaining increasing importance for future prognostic screening of carcinoma patients. Urokinase-type plasminogen activator receptor (uPA-R) is one example of a potential aggressive marker for those cells. However, a valid and reliable double staining method is needed. Using monoclonal antibodies against uPA-R and CK18, we modified an immunogold/alkaline phosphatase double staining protocol. UPA-R/CK18-positive tumor cell controls exhibited black uPA-R staining in 15-80% of cases and red CK18 staining in almost 100% of tumor cells. Isotype-and cross-matched controls were completely negative. Bone marrow from healthy donors was always CK18-negative. Reproducibility of CK18-positive cell detection was estimated in a series of specimens from 61 gastric cancer patients comparatively stained with the single alkaline phosphatase-anti-alkaline phosphatase (APAAP) and our double staining method (10 6 bone marrow cells/patient). In four cases, double staining could not reproduce CK18-positive cells. In 34 cases it revealed fewer or equal numbers, and in 23 cases more CK18-positive cells than the APAAP method. Overall quantitative analysis of detected cell numbers (838 in APAAP, range 1-280 in 10 6 ; double staining 808, range 0-253) demonstrated relative reproducibility of APAAP results by double staining of 97%. Correlation of results between both methods was significant ( p Ͻ 0.001, linear regression). Sensitivity of double staining tested in logarithmic tumor cell dilutions was one CK18-positive cell in 300,000. Specific uPA-R staining was seen on CK18-positive cells in bone marrow from 29 of 61 patients, and also on single surrounding bone marrow cells. To test the specificity of this staining, bone marrow cytospins from 10 patients without tumor disease were stained for uPA-R with the APAAP method. uPA-R expression was confirmed in all 10 cases, with a mean of 6.5% uPA-R-positive cells in 1000 bone marrow cells (SEM 1.2%). These results suggest that our double staining protocol is a sensitive, reproducible, and specific method for routine uPA-R phenotyping of disseminated CK18-positive cells in bone marrow of carcinoma patients.

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“…Progression of human neuroblastoma tumours from the initial stage of transformation of an embryonic precursor cell in the neural crest to advanced stages of metastasis in the nervous system, the adrenal gland and bone marrow has not been well studied in many regards (Brodeur et al, 1988;Gilbert et al, 1988;Brodeur & Moley, 1991;Moss et al, 1991;Thiele, 1991). Little is known about clonal selections that occur at various stages of tumour progression, the routes of tumour cell spread during metastasis, critical genes required for progression, extracellular matrix mechanisms important in these 'events and host cell populations that promote or inhibit these processes.…”

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confidence: 99%

Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: earliest events at ectopic injection sites

Kleinman

Lewandowska²,

Culp³

1994

Br J Cancer

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Prognostic Value of Immunocytologic Detection of Bone Marrow Metastases in Neuroblastoma

Abstract: Immunocytologic analysis of bone marrow aspirates is more sensitive than conventional analysis in detecting tumor cells and provides prognostic information. The relations among marrow metastases, age at diagnosis, and clinical outcome illustrate the biologic heterogeneity of neuroblastoma.

Cited by 218 publications

References 39 publications

Treatment of poor-risk neuroblastoma patients with high-dose chemotherapy and autologous peripheral stem cell rescue

Treatment of poor-risk neuroblastoma patients with high-dose chemotherapy and autologous peripheral stem cell rescue

Immunocytochemical Phenotyping of Disseminated Tumor Cells in Bone Marrow by uPA Receptor and CK18: Investigation of Sensitivity and Specificity of an Immunogold/Alkaline Phosphatase Double Staining Protocol

Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: earliest events at ectopic injection sites

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