Similarities in long-term cultures of blood and bone marrow from patients with acute myelogenous leukemia

1991 ◽  
Vol 9 (5) ◽  
pp. 461-473 ◽  
Author(s):  
Hector Mayani ◽  
Gerald G. Miller ◽  
Anna Janowska-Wieczorek ◽  
A. Robert Turner ◽  
Andrew R. Belch ◽  
...  
Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1474-1482 ◽  
Author(s):  
Anna B. Pawlowska ◽  
Satoshi Hashino ◽  
Hilary McKenna ◽  
Brenda J. Weigel ◽  
Patricia A. Taylor ◽  
...  

To determine whether immune stimulation could reduce acute myelogenous leukemia (AML) lethality, dendritic cells (DCs) were pulsed with AML antigens and used as vaccines or generated in vivo by Flt3 ligand (Flt3L), a potent stimulator of DC and natural killer (NK) cell generation. Mice were then challenged with AML cells. The total number of splenic anti-AML cytotoxic T-lymphocyte precursors (CTLPs) present at the time of challenge was increased 1.9-fold and 16.4-fold by Flt3L or DC tumor vaccines, respectively. As compared with the 0% survival of controls, 63% or more of recipients of pulsed DCs or Flt3L survived long term. Mice given AML cells prior to DC vaccines or Flt3L had only a slight survival advantage versus non-treated controls. NK cells or NK cells and T cells were found to be involved in the antitumor responses of Flt3L or DCs, respectively. DC vaccines lead to long-term memory responses but Flt3L does not. Syngeneic bone marrow transplantation (BMT) recipients were analyzed beginning 2 months post-BMT. In contrast to the uniform lethality in BMT controls given AML cells, recipients of either Flt3L or DC vaccines had a significant increase in survival. The total number of splenic anti-AML CTLPs at the time of AML challenge in BMT controls was 40% of concurrently analyzed non-BMT controls. Flt3L or DC vaccines increased the total anti-AML CTLPs 1.4-fold and 6.8-fold, respectively. Neither approach was successful when initiated after AML challenge. It was concluded that DC vaccines and Flt3L administration can enhance an AML response in non-transplanted or syngeneic BMT mice but only when initiated prior to AML progression.


Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 171-181 ◽  
Author(s):  
WA Bleyer ◽  
RM Blaese ◽  
JS Bujak ◽  
GP Herzig ◽  
RG Jr Graw

Abstract A 19-yr-old boy has been in continuous complete remission from acute myelogenous leukemia for 3 yr after allogeneic bone marrow transplantation prepared with combination chemotherapy. During the first year post-transplant, however, the patient developed near-fatal graft-versus-host reaction followed by 11 severe viral and bacterial infections. Immune evaluation during this period revealed multiple defects which were not present prior to transplantation, nor present in the transplant donor: diminution of lymphoid tissue, decline of all immunoglobulin subtypes, deletion of secretory immunoglobulin, disappearance of isohemagglutinins, loss of antibody to diptheria and tetanus toxoids, cessation of cutaneous hypersensitivity to mumps antigen, and inhibition of serum opsonizing activity. The patient was also unable to develop normal humoral or cellular reactivity to brucella antigen, keyhole limpet hemocyanin, or dinitrochlorobenzene. This patient's course illustrates the severity and chronicity of immunoincompetence associated with allogeneic marrow grafting, the importance of early detection and rigorous treatment of infectious disease in these patients, and the need for improved immunologic reconstitution in human marrow transplantation. It also indicates that complete recovery from the immune defects is possible, and that long- term remission from acute myelogenous leukemia can be achieved with allogeneic marrow transplantation.


Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 171-181
Author(s):  
WA Bleyer ◽  
RM Blaese ◽  
JS Bujak ◽  
GP Herzig ◽  
RG Jr Graw

A 19-yr-old boy has been in continuous complete remission from acute myelogenous leukemia for 3 yr after allogeneic bone marrow transplantation prepared with combination chemotherapy. During the first year post-transplant, however, the patient developed near-fatal graft-versus-host reaction followed by 11 severe viral and bacterial infections. Immune evaluation during this period revealed multiple defects which were not present prior to transplantation, nor present in the transplant donor: diminution of lymphoid tissue, decline of all immunoglobulin subtypes, deletion of secretory immunoglobulin, disappearance of isohemagglutinins, loss of antibody to diptheria and tetanus toxoids, cessation of cutaneous hypersensitivity to mumps antigen, and inhibition of serum opsonizing activity. The patient was also unable to develop normal humoral or cellular reactivity to brucella antigen, keyhole limpet hemocyanin, or dinitrochlorobenzene. This patient's course illustrates the severity and chronicity of immunoincompetence associated with allogeneic marrow grafting, the importance of early detection and rigorous treatment of infectious disease in these patients, and the need for improved immunologic reconstitution in human marrow transplantation. It also indicates that complete recovery from the immune defects is possible, and that long- term remission from acute myelogenous leukemia can be achieved with allogeneic marrow transplantation.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2366-2366
Author(s):  
Courtney D. DiNardo ◽  
Alison Loren ◽  
Steven Goldstein ◽  
Stephen J. Schuster ◽  
Alexander Perl ◽  
...  

Abstract Abstract 2366 Background: Allogeneic hematopoietic stem cell transplant (HSCT) has been shown to be of some benefit for patients with acute myelogenous leukemia (AML) with untreated early relapse. However, outcomes for patients who have morphologic evidence of relapsed leukemia are not well defined. We describe our experience with HSCT for patients with active AML at the time of transplant, to determine prognostic factors for outcome after transplant. Patients and Methods: We analyzed recipients of myeloablative HSCT from 1997 to 2009 at our institution with morphologically active AML at the time of transplant. Patients were identified through our transplant database, and disease status was verified through medical record review. Forty patients were included based on the presence of circulating blasts at the time of admission for transplant, and/or a positive bone marrow biopsy (>5% bone marrow blasts) immediately prior to transplant. There were 6 patients coded as “relapsed/refractory” in our database whose disease status at the time of transplant was unable to be confirmed and thus were excluded from analysis. Results: Baseline patient and transplant characteristics are shown in Table 1. 30% of patients were transplanted for primary induction failure, 22% for first untreated relapse (no treatment between first documented relapse and HSCT), 35% for first refractory relapse (did not attain CR with treatment administered at time of first relapse), and 13% had second or greater refractory relapse. The overall survival for all patients was 82% at 30 days; 55% at 100 days; 28% at one year; and 18% at two years post-HSCT. Of 31 deaths, 71% were attributable to disease, 19% to regimen-related toxicity and infection, and 10% to graft-versus-host-disease (GVHD). Seven patients remain alive at the time of analysis, with 6 patients (15%) alive and free of disease more than 3 years post-HSCT. The median follow-up of the disease-free survivors is 9 years; Table 1 shows characteristics for this subgroup. We identified several patterns of interest. Four disease-free survivors were transplanted in first untreated relapse, yielding 44% (4/9 patients) with first untreated relapse that are long-term disease-free survivors. In addition, while most patients were transplanted with circulating blasts, 5 of 6 disease-free survivors did not have circulating disease. Although 40% of transplants were from unrelated donors, 5 of 6 disease-free survivors received sibling transplants. Conclusions: Our review of patients with morphologically apparent relapsed or refractory AML confirmed that a subset of patients can achieve a durable remission from HSCT. The majority of these long-term survivors shared important characteristics, including (1) lack of circulating blasts at transplant, (2) sibling donors, and (3) first untreated relapse disease status. This information may serve a prognostic purpose, and may assist in identifying appropriate candidates for transplant or for alternative therapies. However, it was not possible based on our analysis to predict reliably those who would not experience long-term survival. Except for second or greater refractory relapse, there was no factor that identified patients who had no benefit from HSCT. As such, HSCT remains a viable option with the potential for long-term disease-free survival in this population. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2267-2267 ◽  
Author(s):  
Jorg Basecke ◽  
Lukas Cepek ◽  
Christine Mannhalter ◽  
Jurgen Krauter ◽  
Stefanie Hildenhagen ◽  
...  

2008 ◽  
Vol 132 (8) ◽  
pp. 1329-1332
Author(s):  
Anna K. Wong ◽  
Belle Fang ◽  
Ling Zhang ◽  
Xiuqing Guo ◽  
Stephen Lee ◽  
...  

Abstract Context.—The clinical association between loss of the Y chromosome and acute myelogenous leukemia and myelodysplastic syndrome (AML/MDS) has been debated because both phenomena are related to aging. A prior publication suggests that loss of the Y chromosome in more than 75% of cells may indicate a clonal phenomenon that could be a marker for hematologic disease. Objective.—To evaluate the relationship between loss of the Y chromosome and AML/MDS. Design.—A retrospective review of cytogenetic reports of 2896 male patients ascertained from 1996 to 2007 was performed. Results were stratified based on the percentage of cells missing the Y chromosome and were correlated with patients' ages and bone marrow biopsy reports through logistic regression analysis with adjustment for age. Results.—Loss of the Y chromosome was found in 142 patients. Of these, 16 patients demonstrated myeloid disease, with 2 cases of AML and 14 cases of MDS. An increased incidence (P < .05) of AML/MDS was seen only in the group composed of 8 patients with complete loss of the Y chromosome in all karyotyped cells (1 case of AML and 7 cases of MDS). Conclusion.—Loss of the Y chromosome appears to be primarily an age-related phenomenon. However, in individuals in which all cells on cytogenetic analysis showed loss of the Y chromosome, there was a statistically significant increase in AML/MDS, suggesting that the absence of any normal-dividing cells in a bone marrow analysis may be indicative of AML/MDS.


Blood ◽  
1997 ◽  
Vol 90 (7) ◽  
pp. 2555-2564 ◽  
Author(s):  
Laurie E. Ailles ◽  
Brigitte Gerhard ◽  
Donna E. Hogge

Abstract Analysis of the mitogenic activity of interleukin-3 (IL-3), Steel factor (SF ), and flt-3 ligand (FL) on acute myelogenous leukemia (AML) blasts using the short-term endpoints of proliferation in 3H-thymidine (3H-Tdr) incorporation assays or methylcellulose cultures (colony assays) showed that greater than 90% of samples contained cells that were responsive to one or more of these cytokines. With this information, culture conditions that were known to support normal long-term culture-initiating cells (LTC-IC) were tested, with or without supplements of one or more of these three growth factors, for their ability to support primitive progenitors from 10 cell samples from patients with AML. In all cases cytogenetically abnormal colony forming cells (CFC) were detected after 5 weeks when AML peripheral blood or marrow cells were cocultured on preestablished, normal human marrow feeders (HMF ) and/or Sl/Sl mouse fibroblast feeders and the number of CFC detected in these 5-week-old LTC maintained a linear relationship to the number of input AML cells. Limiting dilution analysis, performed on 6 of the 10 samples, showed the frequency of AML cells initiating LTC (AML LTC-IC) to be 5- to 300-fold lower than the frequency of AML-CFC in the same cell sample, whereas the average number of CFC produced per LTC-IC varied from 1 to 13. Surprisingly, in each case the concentration of cytogenetically normal LTC-IC detected in AML patient blood was at least 10-fold higher than that previously observed in the blood of normal individuals. “Mixed” mouse fibroblast feeders engineered to produce human G-CSF, IL-3, and SF did not enhance detection of AML LTC-IC but did increase the output of cytogenetically normal CFC from LTC of 3 of 4 patient samples. Supplementation of AML LTC with IL-3 and exogenously provided SF and/or FL increased the output of AML-CFC from 5-week-old LTC by greater than or equal to twofold with 5 of 9 patient samples, whereas in one case exogenous addition of FL reduced the output of malignant CFC from LTC. These studies show that conditions that support normal LTC-IC also allow a functionally analogous but rare AML progenitor cell type to be detected. In addition, differences in the responses of normal and leukemic cells to various cytokines active on normal LTC-IC were revealed. Further analysis of these differences may enhance our understanding of leukemogenesis and lead to observations that could be exploited therapeutically.


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