Xenotransplantation of hematopoietic cells resistant to HIV as a potential treatment for patients with AIDS.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
E D Ball
Publications and source records attributed to E D Ball.
Autologous bone marrow transplantation for adult acute leukemia.
In this review we have considered the role of ABMT for the acute leukemias. It is apparent from data around the world that ABMT is a curative therapy for patients with both AML and ALL after primary treatment failure. Other than allogeneic BMT, ABMT may be the only curative therapy following relapse, especially in AML. The role of ABMT in first CR is less well defined. There are few data to support the widespread use of ABMT in first CR for ALL. Moreover, the improved survival of adults with ALL with current intense multiagent regimens will probably obviate the need to continue clinical trials of ABMT for ALL in first CR. For patients with AML in first CR, however, it seems that ABMT may well lead to improved rates of DFS compared with chemotherapy alone. Almost every published report describes better DFS for patients who underwent ABMT compared with historical or contemporary controls who were treated with chemotherapy. One note of caution is that as chemotherapy evolves, the increment in survival currently observed from ABMT may diminish, thus rendering ABMT less obviously necessary. On the other hand, from an economic standpoint, ABMT could prove to be cost-effective, because a short, intense treatment that is effective may prove to be less costly than the current extended period of chemotherapy. Because ABMT is becoming safer, it would seem reasonable to continue its use in patients with AML at high risk for relapse (secondary AML, adverse cytogenetics, and so on) while awaiting the outcome of the randomized clinical trials currently underway that are seeking to define the role of ABMT for the general population of patients with AML after initial remission is achieved. Meanwhile, further definition of the relative value of the various purging regimens, preparative regimens, and adjunctive therapy (i.e., IL-2, mAb) warrants study.
Acute Disease↗
ras oncogene activation and occupational exposures in acute myeloid leukemia.
BACKGROUND: Epidemiologic studies of acute myeloid leukemias (AMLs) show small increases in risk of disease associated with certain occupations and chemical exposures. PURPOSE: This study was designed to determine whether the presence of mutationally activated ras oncogenes in AML are associated with occupational and chemical exposures. METHODS: We interviewed 62 patients with newly diagnosed AML (or their next-of-kin), all of whom were enrolled in a national multicenter clinical trial, and 630 healthy control subjects. DNA extracted from patients' pretreatment bone marrow samples was amplified by using the polymerase chain reaction and probed with allele-specific oligonucleotides for activating point mutations at the 12th, 13th, and 61st codons of three protooncogenes: H-ras (also known as HRAS), K-ras (also known as KRAS2), and N-ras (also known as NRAS). RESULTS: Patients with ras mutation-positive AML had a higher frequency (six of 10 patients) of working 5 or more years in an a priori high-risk occupation than did patients with ras mutation-negative AML (eight of 52; odds ratio [OR] = 6.8; 95% confidence interval [CI] = 1.3-36). Patients with ras mutation-positive AML were more likely than patients with ras mutation-negative AML to have breathed chemical vapor on the job (OR = 9.1; 95% CI = 1.3-64) or to have had skin contact with chemicals (OR = 6.9; 95% CI = 1.3-37). When ras-positive patients were compared with healthy control subjects, the ORs for occupation and occupational exposures remained elevated, while patients with ras mutation-negative AML showed no increased risk when compared with control subjects. CONCLUSION: Activation of ras proto-oncogenes may identify an etiologic subgroup of AML caused by occupation and chemical exposure. IMPLICATION: Disease etiology may be better understood if epidemiologic measures of exposure are integrated with molecular assays of the genetic defects responsible for cancer initiation and promotion.
Acute Disease↗
Initial trial of bispecific antibody-mediated immunotherapy of CD15-bearing tumors: cytotoxicity of human tumor cells using a bispecific antibody comprised of anti-CD15 (MoAb PM81) and anti-CD64/Fc gamma RI (MoAb 32).
The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)
Antibodies, Monoclonal↗
Engraftment of leukocyte subsets following autologous bone marrow transplantation in acute myeloid leukemia using anti-myeloid (CD14 and CD15) monoclonal antibody-purged bone marrow.
The cell surface phenotype of leukocyte subsets during reconstitution following autologous bone marrow transplantation (ABMT) using bone marrow purged with anti-myeloid monoclonal antibodies (MoAbs) and complement (C') was evaluated in 20 patients with acute myeloid leukemia (AML). Repopulation of B and T lymphocytes, natural killer (NK) cells, and myeloid cells was assessed by phenotypic analysis using two-color cytofluorography of peripheral blood mononuclear cells (PBMNC) at several time points up to 2 years post-transplantation. In spite of removal of the majority of monomyeloid cells of the autograft by purging with anti-CD14 and anti-CD 15, engraftment occurred rapidly. The myeloid cells appeared normal by surface phenotype. An early rise in NK cells, characterized by expression of CD57 and CD 16, was seen. The CD4:CD8 ratio remained low throughout the study period, primarily due to a persistently low CD4 level. ABMT using bone marrow purged with the anti-myeloid MoAbs PM-81 and AML-2-23 and C' resulted in prompt engraftment of neutrophils. Although there was a prolonged time for recovery of lymphocyte subsets, this did not result in an increased risk of early infectious complications. Late infectious complications post-transplantation were limited to herpes zoster infection in one patient 18 months post-transplantation, and bacterial meningitis in that same patient 2 months later. This study demonstrates that ABMT in patients with AML using bone marrow purged with the anti-myeloid MoAbs PM81 (anti-CD15) and AML-2-23 (anti-CD14) and C' results in rapid hematologic engraftment and delayed phenotypic immunologic reconstitution without significant acute or chronic clinical toxicities.
Adolescent↗
Predictive value of flow cytometric analyses of blast cells in assessing the phenotype of the leukemia colony-forming cell (L-CFC) population in acute myeloid leukemia.
Acute myeloid leukemia (AML) blast cells (BC) express antigens that are commonly found on their normal counterparts. The leukemia colony-forming cell (L-CFC) subpopulation, identified by its ability to form leukemia colonies in vitro, is thought to be the stem cell population that produces BC. To ascertain the association between myeloid antigens on the BC and the L-CFC from the same patient, we compared the expression of CD14, CD15, CD33, p124 and HLA class I from 17 cases of AML. These particular myeloid antigens were studied because they are suitable targets in purging bone marrow for autotransplantation. We found no significant difference in the expression of CD14, CD15, CD33, and HLA class I on the BC and L-CFC from the same patient, although we observed considerable heterogeneity among different AML cases. Analysis of the progenitor cell antigen p124 revealed significant within-patient differences on the BC and L-CFC (p = 0.007), with a greater tendency for expression on the L-CFC. This heterogeneity may be due to differences in maturation stage of the L-CFC and BC. This information is important when L-CFC phenotype is used to determine the appropriate selection of antibodies for purging of residual disease in the context of auto-transplantation.
Antigens, Differentiation↗
Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow.
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Adolescent↗
Isodicentric chromosome 18q as sole abnormality in a histologically normal bone marrow from a patient with diffuse large-cell non-Hodgkin's lymphoma.
Cytogenetic analysis was performed on the histologically and immunophenotypically normal bone marrow (BM) of a 33-year-old woman with non-Hodgkin's lymphoma (NHL) before BM harvest. Unstimulated 24- and 48-hour cultures produced only normal metaphases. A pokeweed mitogen (PWM)-stimulated 48-hour culture, however, showed a clonal isodicentric chromosome 18q as the sole abnormality, suggesting a role for this approach in detection of submicroscopic BM involvement by B-cell NHL.
Adult↗
Prognostic value of lymphocyte surface markers in acute myeloid leukemia.
We studied the expression of cell surface antigens associated with myeloid and lymphoid leukemias on bone marrow-derived blast cells from 339 patients with newly diagnosed de novo acute myeloid leukemia (AML) enrolled on Cancer and Leukemia Group B (CALGB) chemotherapy protocols. Surprisingly, of 211 cases studied for the expression of CD2 (T-cell marker, sheep erythrocyte binding receptor for T lymphocytes) 45 were positive (21%). In addition, of 298 patients studied for CD19 (B-lymphocyte marker), 41 were positive (14%). Overall, of 170 patients studied for both CD2 and CD19, 56 (33%) were positive. Interestingly, central review of the French-American-British (FAB) morphology of the CD2- and CD19-positive cases showed that FAB M3 was twice as frequent, and M4E eight times as frequent compared with the CD2- and CD19-negative cases. Of 22 lymphocyte antigen-positive cases in which cells were available for studies of Ig or T-cell antigen receptor (TCR) gene rearrangement, 20 were germline, one had a rearranged Ig heavy chain gene, and one had rearranged TCR beta and Ig heavy chain genes. The presence of messenger RNA for CD2 was demonstrated in four CD2 surface antigen-positive cases, thus validating the cell surface data. Lymphocyte antigen-positive cases had karyotypes commonly seen in AML; 71% of cases with an abnormal clone had t(8;21)(q22;q22), inversion 16(p13q22), t(15;17)(q22;q12), or t(9;11)(p22;q23). The patients with lymphocyte markers had a significantly higher incidence of these karyotypic abnormalities compared with patients with lymphocyte antigen-negative AML (34% v 15%, P less than .02). When the outcome to therapy of the lymphocyte antigen-positive cases was compared with that for the CD2, CD19-negative cases, we found that the CD2, CD19-positive cases actually had higher complete remission rates (75% v 59%, P = .04), and significantly longer time to failure (P = .02; 32.4% +/- 6.0% v 18.0% +/- 4.1% at 2 years) and overall survival (P = .02; 43.5% +/- 6.3% v 26.0% +/- 4.5% at 2 years). CD2 antigen-positive cases also had a significantly superior survival (P = .02; 43.8% +/- 7.9% v 29.8% +/- 3.8% at 2 years). There were no significant differences (P less than or equal to .05) between the two groups in age, leukocyte count at diagnosis, incidence of extramedullary disease, or FAB classification.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Reactivity of anti-CD15 monoclonal antibody PM-81 with breast cancer and elimination of breast cancer cells from human bone marrow by PM-81 and immunomagnetic beads.
The CD15 carbohydrate antigen, lacto-N-fucopentaose III is expressed on a variety of human cancer cells including acute myeloid leukemia, small cell carcinoma of the lung, and colorectal carcinomas. We have found that cells from breast cancer cell lines and patient-derived tissue are strongly CD15 positive, as seen by binding to the PM-81 monoclonal antibody. In this report we show that monoclonal antibody PM-81 and immunomagnetic beads can remove breast cancer cells from bone marrow and thus be used as "purging" agents for autologous bone marrow transplantation. PM-81 and immunomagnetic beads removed up to 3 log of SK-BR-3 and MCF7 breast carcinoma cell line cells while minimally affecting normal hematopoietic progenitor cells. This technique may be useful for purging marrow for autologous bone marrow transplantation in breast cancer.
Antibodies, Monoclonal↗
Expression of the CD15 antigen on normal and leukemic myeloid cells: effects of neuraminidase and variable detection with a panel of monoclonal antibodies.
Normal and malignant myeloids cells are known to express cell surface molecules having in common the carbohydrate antigen lacto-N-fucopentaose-III (LNF-III--termed CD15). We used flow cytometry to examine the variability of CD15 expression in normal cells and acute myeloid leukemia (AML) cells as detected by 24 murine monoclonal antibodies (mAb). Important differences in the levels of binding were observed with the various mAb. Titrations of each mAb were performed to confirm that these differences in binding were due to increased antigen detection and not differences in concn. In studies of CD15 expression on AML cells selected from a large prospective study, anti-CD15-1 (also known as PM-81) showed the highest binding to each case. Neuraminidase was added to cells from seven AML patients that we had previously found to be low in CD15 expression, in order to determine if cryptic CD15 was present on these cells. Neuraminidase enhanced binding of each of the entire panel of mAb on five patients' cells, thus demonstrating the ubiquitous expression of CD15 on AML cells. In two cases, binding of only some of the mAb was increased, indicating exposure of unusual epitopes on those cells. Subpopulations of normal peripheral blood lymphocytes, cells not associated with CD15 expression, also substantially increased their level of binding to some of the mAb after the addition of neuraminidase. Two-color flow cytometry was used to determine the immunologic phenotype of the lymphocytic population that expressed CD15. This technique revealed that 9.5% normal lymphocytes coexpressed the CD15 and CD3 (T cell) antigens. In addition, by gating on large granular lymphocytes we found that 24.4% of these cells coexpressed CD15 (detected by PM-81) and CD2 (sheep erythrocyte receptor), while 50.3% expressed CD15 and CD16 (type III Fc receptor, natural killer cell-associated). This is consistent with the notion that sialylated CD15 is expressed on some natural killer cells and T cells.
Antibodies, Monoclonal↗
Immune markers in hematologic malignancies.
The precise delineation of biologic traits that distinguish normal hematopoietic cells from their malignant counterparts is of fundamental importance in understanding all aspects of hematologic malignancies. An increasingly sophisticated technologic battery has been utilized to dissect out these differences--primarily utilization of monoclonal antibodies, by immunoperoxidase, immunoalkaline phosphatase and flow cytometric techniques. An even more basic understanding of normal and malignant hematopoietic cells has begun to evolve as molecular biology begins to unravel gene misprogramming by Southern and Northern blot analysis and the polymerase chain reaction. These techniques not only help distinguish a normal cell from a malignant one, but characterize the malignant clone as B-lymphoid, T-lymphoid or myeloid and allow further subcategorization within these broad lineages. These distinctions are vital to the entire spectrum of basic and clinical research involving hematologic malignancies and are assuming an increasingly important role in their diagnosis, prognosis and treatment.
Antibodies, Monoclonal↗
Purging of small cell lung cancer cells from bone marrow using immunomagnetic beads and a flow-through device.
Immunomagnetic beads can be used to remove subpopulations of cells from a mixed cell suspension in a flow-through system. One application of this process is the removal of tumor cells from bone marrow prior to its use in autologous bone marrow transplantation (ABMT). Based on preliminary data showing that three monoclonal antibodies (MoAb) (SCCL 175, HNK-1, and TFS-4) gave optimal separation in small-scale experiments, we have designed a large-scale separator suitable for clinical use. In our separator, the cell suspension flows through a 150 ml baffled transfer pack which is held over an array of permanent magnets. Direct (one MoAb only) and indirect (MoAb and anti-mouse antibody) methods of binding beads to cells were investigated as were the effects of temperature, bead to cell ratio, and medium additives on tumor cell removal and normal cell recovery. We determined the optimal separation conditions to be the indirect method of binding at 22 degrees C using a bead to tumor cell ratio of 25:1. Testing of the device on DMS-273 small cell lung cancer (SCCL) cells mixed with normal human bone marrow mononuclear cells resulted in a mean tumor cell removal of 3.64 logs (99.977%) with a concomitant mean normal granulocyte-monocyte colony forming unit (CFU-GM) recovery of 61.3%. These experiments form the basis to use the immunomagnetic beads to purify bone marrow from patients with SCCL for use in ABMT.
Antibodies, Monoclonal↗
Elimination of small cell carcinoma of the lung from human bone marrow by monoclonal antibodies and immunomagnetic beads.
The majority of patients with small cell carcinoma of the lung (SCCL) have bone marrow involvement detected by monoclonal antibodies (mAb). High dose chemotherapy followed by autologous bone marrow transplantation may improve treatment results for patients with SCCL, but the bone marrow may need to be purged of contaminating tumor cells. This study investigates the reactivity of a panel of mAb with two SCCL cell lines and normal bone marrow and the ability of the mAb and immunomagnetic beads to eliminate the SCCL cells from a mixture of 90% normal bone marrow cells and 10% SCCL cells. The mAb and immunomagnetic beads removed 4 to 5 log of SCCL cells in the model system. The immunomagnetic separation did not significantly adversely affect normal hematopoietic progenitor cells, as determined by bone marrow colony-forming units. The results suggest that the mAb and immunomagnetic beads could safely and effectively separate SCCL cells from the bone marrow for autologous bone marrow transplantation following high dose chemotherapy.
Antibodies, Monoclonal↗
Trisomy 13: a new recurring chromosome abnormality in acute leukemia.
A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias.
Acute Disease↗
Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow.
We report our experience from a clinical trial of autologous bone marrow transplantation (ABMT) in the treatment of 30 patients with acute myeloid leukemia (AML) using monoclonal antibody (MoAb) and complement-treated bone marrow. All patients were in complete remission (CR) at the time of transplant: 6 patients were in first CR, 18 in second CR, and 6 in third CR. The median age of all patients was 42 years (range 11 to 57 years). For marrow ablation, 28 patients were treated with cyclophosphamide and total body irradiation. One patient was treated with busulfan and cyclophosphamide and one was treated with busulfan and VP-16. Each patient was then transfused with autologous bone marrow that had been harvested previously and treated with two MoAbs, PM-81 and AML-2-23, and rabbit complement. Median time to recovery of neutrophils (500/microL) was 30 days, and platelets (20,000/microL) was 45 days. Median time for initial erythrocyte engraftment, assessed by a flow cytometric reticulocyte assay, was 13 days. Median overall and relapse-free survival of first CR patients was at least 17.4 months post-ABMT and the 2- and 3-year actuarial overall and relapse-free survival was 67% (+/- 19%). Median survival for the 24 patients in second or third CR was 6.8 months post-ABMT and 9.3 months since CR; however, six patients survived disease-free from 16 to 61 months post-ABMT. For the second and third CR group it was observed that six patients (5 of the 6 survivors) showed "inversions," when their post-ABMT remission lasted longer than any previous one. Actuarial 2- and 3-year disease-free and overall survival of patients in second and third CR was 25% (+/- 9%) and 18% (+/- 9%), and 29% (+/- 9%) and 23% (+/- 9%), respectively. ABMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation.
Adolescent↗
Induction of differentiation in blast cells and leukemia colony-forming cells from patients with acute myeloid leukemia.
The characteristic lesion in acute myeloid leukemia (AML) is the failure of myeloid cells to differentiate normally, leading to the accumulation of immature blast cells (BC) in the bone marrow. We determined whether BC and leukemia colony-forming cells (L-CFC) from AML patients could differentiate in vitro after short-term culture with interferon-gamma (IFN gamma), 1,25 dihydroxyvitamin D3 (D3), retinoic acid (RA), tumor necrosis factor-alpha (TNF alpha), and granulocyte-monocyte colony-stimulating factor (GM-CSF). Expression of myeloid differentiation antigens CD15, CD14, CD33, and p124 was determined on the BC by immunofluorescence and on the L-CFC by monoclonal antibody (MoAb) and complement (C')-mediated cytotoxicity followed by cloning in methylcellulose. We found that 26 of 39 (67%) cases demonstrated changes in the expression of myeloid differentiation antigens on the BC, and 6 of 7 (86%) cases showed an altered L-CFC myeloid antigen phenotype after short-term culture with differentiating agents. Alterations in myeloid antigen expression in the L-CFC population correlated with a reduction in L-CFC cloning potential. In the BC, alterations of myeloid differentiation antigens occurred in a manner consistent with those observed during normal myelopoiesis. For example, CD14 antigen expression (a late-stage monocyte antigen) increased on BC from 12 of 39 (31%) cases, and p124 (an antigen expressed both by myeloid progenitor cells and by a subset of monocytes) increased on 15 of 39 (38%) cases. Changes in the expression of CD33 antigens (expressed normally by myeloid progenitor cells and by mature monocytes) on the BC were variable, with 7 of 29 cases (24%) showing a decrease and 7 of 29 cases (24%) showing an increase. When comparisons were made between pairs of differentiation agents that caused the altered expression of an antigen on either the BC or L-CFC of a patient, the majority of changes were in the same direction (either both "increased" or both "decreased"). This suggests that the direction of antigen change is characteristic of the leukemia cell subpopulation for each patient and not of the stimulatory agent. This study demonstrates that cells from more than two thirds of AML cases examined responded to various differentiation agents in vitro as measured by changes in the expression of myeloid cell-associated surface antigens and by alterations in cloning potential of the L-CFC, a finding of potential clinical significance.
Antigens, CD↗
Autologous bone marrow transplantation in the treatment of acute myeloid leukemia: the Dartmouth experience and a review of literature.
Autologous bone marrow transplantation is increasingly being investigated as a treatment for patients with acute myelogenous leukemia. Review of the literature demonstrates that much of the data are incomplete. Most reports contain small numbers of patients, making analysis of any particular regimen difficult to assess. The morbidity and mortality of the procedure appear to be substantially less than that seen in the allogeneic setting. The major complications relate to problems with engraftment. Recovery of platelet production to normal levels is frequently cited as delayed, and in some patients, does not occur. This phenomenon may be heightened by marrow manipulation during purging or posttransplant drug therapy. It is not known if this is a problem related to stem cells or related to the changes in the hematopoietic microenvironment. The results of autologous bone marrow transplantation for patients with acute myeloid leukemia suggest that, as with standard chemotherapy, there is little survival benefit when patients are in relapse at the time of transplantation. There are few long-term survivors, and relapse within 5 months is the rule. It should be noted that the vast majority of the studies reported here have used marrow that has not been treated in an attempt to remove occult leukemia cells. The use of purged bone marrow has not yet been adequately studied. In patients in second or subsequent remission, ABMT appears to offer a chance for long-term survival not seen with present second-line standard chemotherapy regimens and should be considered a viable option for patients under the age of 55. The results to date do not define whether marrow purging is beneficial, and most studies being carried out at the present time are not evaluating this question. The majority of studies are examining different methods of purging. The result of our study in patients in second and third remission using in vitro purging of bone marrow with monoclonal antibodies PM-81 and AML2-23 are encouraging, as are the studies of purging with 4-HC. The Cancer and Leukemia Group B has just begun a study for patients with AML in second remission using the protocol we piloted at Dartmouth. We are also evaluating the feasibility of using this therapy in patients at the time of first relapse, as studies in the allogeneic setting have suggested the results are similar to those achieved in second remission (60).(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗