Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study has been in progress since June 1985 to evaluate the use of myeloablative therapy (cyclophosphamide [60 mg/kg x 2] and total body irradiation [200 cGy x 6]) followed by reinfusion of autologous bone marrow in patients in second or subsequent remission of B-cell non-Hodgkin's lymphoma. The marrow mononuclear cell fraction is being treated in vitro with three cycles of the monoclonal antibody anti-CD20 (anti-B1, Coulter Immunology) and baby rabbit complement (Pel-Freez). Thirty-eight patients with follicular lymphoma (age range 29-61 years, median 43) have been treated to date. At the time of treatment, 28 patients were in second remission, 7 were in third, and 3 were in more than third remission. Twenty-three patients were in complete remission, 15 had residual disease (7 had lymph nodes less than 2 cm diameter, 4 had less than 10% bone marrow infiltration, 1 had involvement of lymph nodes and bone marrow, and 3 had involvement at other sites). Of the 38 study patients, 32 are alive; 6 have died, 4 in remission. Two of the deaths were treatment related: 1 resulted from cerebral haemorrhage at 29 days; 1 resulted from systemic fungal infection at three months). One patient died from secondary acute myelogenous leukaemia at four years, and another from an unrelated cause. Two patients died following relapse. The median time to engraftment was 28 days (range 15-45 days) for neutrophils greater than 0.5 x 10(9)/L and 28 days (range 15-46 days) for platelets greater than 20 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myeloablative therapy with autologous bone marrow transplantation as consolidation of remission in patients with follicular lymphoma. 204 12

A better understanding of the immunobiology after transplantation and of the available recombinant cytokines that enhance hematopoietic reconstitution following autologous and allogeneic bone marrow transplantation is likely to result in safer application of bone marrow transplantation. Residual tumor cells escaping chemotherapy or chemoradiotherapy given in the course of autologous and allogeneic bone marrow transplantation are still a barrier to complete eradication of malignancy. Recent experiments in animal models of human disease suggest that minimal residual disease can be controlled by an innovative therapy consisting of the administration of cytokines such as recombinant human interleukin-2 and interferon-alpha. Moreover, graft versus leukemia-like effects are induced in conjunction with autologous and allogeneic bone marrow transplantation by administration of allogeneic immunocompetent lymphocytes and recombinant interleukin-2 following bone marrow transplantation and especially by combined administration of allogeneic lymphocytes and recombinant interleukin-2. Similar approaches are currently being investigated in humans with encouraging preliminary results. Overall, our data suggest that eradication of the last tumor cell is neither feasible nor necessary for achieving operational cure. Control of minimal residual disease by activation of anticancer effector cells today seems closer than ever and we are optimistic that further advances in immunotherapy will be applicable to clinical practice in the near future.
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PMID:New developments in bone marrow transplantation. 206 90

The potential of various photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants is discussed in this paper. The results with fluorescent dyes, Dihematoporphyrin Ether (DHE) and Merocyanine-540 (MC-540) are detailed. Following photoradiation of cells with white light, both DHE and MC-540 showed high cytocidal activity towards lymphoid and myeloid neoplastic cells, but had significantly less effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E) and mixed colony-forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL-60), non-B, non-T, cALLa positive acute lymphoblastic leukemia (Reh), and diffuse histiocytic B-cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 ug/ml and MC-540 concentrations of 15 to 20 ug/ml, clonogenic tumor cells could be reduced by more than 4 logs, when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells, and on normal marrow myeloid (CFU-GM) precursors, when the drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15-20 ug/ml) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). Using DHE (2.5 ug/ml), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared, following sequential drug and light exposure of cells, while simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. The data from various centers is briefly discussed with special emphasis on clinical trials. Our results provide a useful model for leukemia and lymphoma cells and suggest that these phototherapy experiments can be implemented into clinical trials.
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PMID:Photoradiation methods for purging autologous bone marrow grafts. 213 34

Reviewed in this study are 40 patients treated by high-doses of alkylating agents followed by autologous marrow rescue for ovarian cancers. All patients received this therapy after extensive surgery and a median of 6 cycles of CDDP containing regimens (CAP or CHAP). All patients, except 4, who showed evidence of progression, had a second surgical exploration before the high dose chemotherapy. Conditioning regimens consisted of: melphalan at a dosage greater than 140 mg/m2 for all patients; in addition, 2 received Endoxan 120 mg/kg and 1 busulfan 16 mg/kg. Autologous marrow rescue was infused 24 h after the conditioning regimen. Severe, but reversible aplasia and mucositis were the most common toxicities. Three patients died from this procedure, 2 from infection and 1 from secondary leukemia. Twelve out of 15 patients evaluated responded (80%) showing evidence of activity in patients who did not respond to first line chemotherapy. Duration of response was short, especially for patients treated for progressive disease rather than in partial or complete response at the time of high doses chemotherapy. With a median follow up of 23 months (range 8.54) 19 patients survived (15 with non-evolutive disease) leading to a projected survival rate of 39% between 27 months and 5 years. These results are encouraging for poor risk patients who failed to respond to initial chemotherapy. For patients who have small or no residual disease after initial therapy, the place of such intensification should be confirmed prospectively in a larger cohort of patients.
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PMID:[High doses of alkylating agents and bone marrow autograft in ovarian cancer with poor prognosis: a retrospective analysis of 40 patients treated in France]. 215 87

The occurrence of Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukaemia (AML) following cytotoxic therapy for neoplastic disease is well recognised. RAS mutations are common in patients with MDS and AML. To determine whether these lesions are found as early markers of secondary disease, we have studied the incidence of RAS mutations in the peripheral blood of 70 patients in complete remission from lymphoma. Patients were treated by standard chemotherapy regimes and/or localised radiotherapy. Treatment had been given 6 months to 14 1/2 years previously and no patient showed any sign of residual disease. Genomic DNA from peripheral blood leukocytes was amplified in vitro at target codons of N, K and H RAS genes, and mutations detected by hybridisation with oligonucleotide probes. RAS mutations were detected in 9 subjects. One patient with an N12 valine (Val) substitution had been in complete remission from Hodgkin's disease (HD) for 9 years. DNA from this patient registered in a nude mouse tumorigenicity assay (NMT). The N12 Val mutation was not detected in the original tumour tissue from the same patient. A second patient in remission from HD showed evidence of co-existent N12 cysteine (Cys) and N13 valine (Val) substitutions which were not detected in presentation material or unaffected tissues. All patients are currently haematologically normal, indicating that clones of mutant RAS bearing cells may be detected prior to any overt sign of disease.
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PMID:RAS mutations in patients following cytotoxic therapy for lymphoma. 217 19

Fourteen patients with high-risk T-lineage acute lymphoblastic leukemia (ALL) in complete remission underwent autologous bone marrow transplantation (BMT) in an attempt to eradicate their residual disease burden. A combined immunochemotherapy protocol using a cocktail of two immunotoxins directed against CD5/Tp67 and CD7/Tp41 T-lineage differentiation antigens in combination with the in vitro active cyclophosphamide congener 4-hydroperoxy-cyclophosphamide (4-HC) was used to purge autografts. Despite high dose pretransplant radiochemotherapy and effective purging of autografts, 9 of 14 patients relapsed at a median of 2.5 months (range, 1.2 to 16.8 months) post BMT. Two patients remain alive and disease free at 26 and 28 months post BMT. We used a novel quantitative minimal residual disease (MRD) detection assay, which combines fluorescence activated multiparameter flow cytometry and cell sorting with leukemic progenitor cell (LPC) assays, to analyze remission bone marrow (BM) samples from T-lineage ALL patients for the presence of residual LPCs. Notably, high numbers of residual LPC detected in remission BM before BMT constituted a poor prognostic indicator, providing the first evidence for the biologic significance and clinical value of in vitro T-lineage ALL LPC assays. The median value for the residual leukemia burden before BMT, was approximately 8.6 x 10(3) LPC/10(8) mononuclear cells (MNC) (approximately 0.0086% LPC). Patients with a residual leukemia burden less than this median value appeared to have a better outlook for remaining free of relapse after autologous BMT than patients with a greater leukemia burden (53 +/- 25% v 14 +/- 13%, P = .006, Mantel-Cox). By comparison, the log kill efficacy of purging, the remaining numbers of LPC in purged autografts, or the estimated numbers of reinfused LPC, did not correlate with the probability of disease-free survival (DFS). These results indicate that the primary reason for the recurrence of leukemia was inefficient pretransplant radiochemotherapy rather than inefficient purging of autografts.
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PMID:Autologous bone marrow transplantation in high-risk remission T-lineage acute lymphoblastic leukemia using immunotoxins plus 4-hydroperoxycyclophosphamide for marrow purging. 222 22

Morphologic, immunologic, enzymatic and cytogenetic methods detect residual leukemic cells at the level of 5%. The early detection of leukemia by these methods has failed to improve outcome for children with residual disease. The use of molecular biologic techniques, particularly those involving the polymerase chain reaction, can detect 1 leukemic cell among 10,000 or even 100,000 normal cells. At this time, it is essential to conduct the proper clinical trials to determine the clinical utility of methods so sensitive and specific.
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PMID:Detection of minimal residual leukemia in acute lymphoblastic leukemia. 226 84

The newly produced monoclonal antibody (mAb) LF61 detects a molecule restricted to hairy cell leukaemia (HCL) among B-cell non-Hodgkin's lymphomas. In particular, the percentage of LF61 + HCL cells in different cases ranges from 10% to 100%. In normal lympho-haemopoietic tissues LF61 reacts with only about 2% of T-cells, mostly of the CD8 subset in the peripheral blood, extrafollicular areas of the tonsil, red pulp of the spleen and thymic medulla. Expression of the LF61 molecule is observed following stimulation of peripheral blood lymphocytes with phytohaemagglutinin (PHA) or pokeweed mitogen (PWM), suggesting that it represents an activation antigen. Due to its restricted reactivity with a small subset of normal CD8 + T-cells, LF61 in combination with a CD22 mAb is highly suitable for monitoring residual disease in interferon or deoxycoformicin-treated HCL patients. Polyacrylamide gel gradient electrophoresis shows that LF61 precipitates a 150 kDa, 125 kDa, 105 kDa trimeric molecule from the surface of HCL cells. Immunohistological and immunobiochemical results show that this molecule is the same as the one recognized by the still unclustered anti-HCL mAb B-ly7.
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PMID:LF61: a new monoclonal antibody directed against a trimeric molecule (150 kDa, 125 kDa, 105 kDa) associated with hairy cell leukaemia. 226 7

One of the objectives of Childrens Cancer Study Group (CCSG) study 141 (CCG-141) was to determine the frequency of occult testicular leukemia (TL) after 3 years of disease-free survival (DFS) and to retreat boys with occult TL to prolong their subsequent DFS. Of the 494 boys entered on study, 255 (51.6%) were in complete continuous remission (CCR) 3 years after entering remission and an additional eight were in CCR 3 years after localized extramedullary relapse and retreatment; 263 boys were eligible for testicular biopsy. Elective testicular biopsy was performed on 235 (89.4%) boys. Of the 204 (86.8%) boys with negative biopsies, 175 (85.8%) remained in CCR 10 to 12 years after diagnosis and 25 (12.3%) relapsed, 11 (44%) of whom died. Isolated overt TL occurred in four (2.0%) and all remained in CCR 22+ to 60+ months after re-treatment. Of the 26 boys with occult TL, 16 (62%) remained in CCR. Ten (38%) relapsed despite local testicular irradiation and systemic re-treatment; six of the 10 died. Of the 26 boys who did not undergo biopsy, 21 (80.8%) remained in CCR; two (7.7%) developed isolated overt TL. DFS after testicular biopsy was significantly better in boys without occult TL (P = .001). Occult TL after 3 years of CCR represents aggressive minimal-residual disease and carries a worse prognosis than absence of TL. Initial treatment should be directed at obviating occult and overt testicular relapse. Conventional therapy as used in this study was suboptimal in preventing subsequent bone marrow (BM) relapse and death. If occult TR is identified during or at the end of planned therapy, a higher salvage rate may require intensified alternate therapy. As such, testicular biopsies may be clinically useful. Further investigation is limited by the relative rarity of, and the lack of identifying features in boys with occult TL.
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PMID:The prognostic value of testicular biopsy in childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group. 229 11

Although high-dose chemoradiotherapy used for conditioning prior to autologous bone marrow transplantation (BMT) represent an effective tool for eradication of certain malignant hematological disorders, relapses indicate that the last tumor cell is unlikely to be completely eradicated. We are investigating several approaches for controlling residual tumor cells escaping from chemoradiotherapy by cellular adoptive immunotherapy and amplification of natural defense mechanisms, using recombinant human IL2 (Cetus, Emeryville CA), in a murine model of leukemia/lymphoma disease (BCL1).
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PMID:Immunotherapy in conjunction with autologous bone marrow transplantation. 231 4


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