Peripheral Blood and Bone Marrow Derived Dendritic Cells in Acute Myelogenous Leukemia

Author(s):  
K. Kratz-Albers ◽  
J. Kienast ◽  
H. Ostermann ◽  
R. Leo ◽  
Th. Büchner ◽  
...  
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.


2007 ◽  
Vol 131 (8) ◽  
pp. 1281-1289
Author(s):  
Farah Khalil ◽  
Hernani Cualing ◽  
Julia Cogburn ◽  
Lili Miles

Abstract Context.—Although the early post–myelosuppressive chemotherapy pathologic changes of the marrow have been described, the rate and the histologic definition of recovery are not defined. Objective.—To study the rate of recovery of bone marrow in patients given myelosuppressive therapy for acute myelogenous leukemia, establish the histologic criteria of recovered marrow, and correlate the recovery pattern with those patients who received a bone marrow transplant by using histology, peripheral blood, immunophenotyping, and computerized morphometry and mathematical slope equation. Design.—We studied the post–myelosuppression recovery of the bone marrow to determine patterns and rate of recovery in 135 serial bone marrow biopsies of 51 patients. These patients were divided into 2 groups: 1 group of 28 cases diagnosed with acute myeloid leukemia, the majority treated with cytarabine (Ara-C) infusion for 7 days and daunorubicin intravenously daily for 3 days (7+3 regimen), and the other control group of 23 cases treated with chemotherapy or allogeneic bone marrow transplantation for a variety of hematologic malignancies. All biopsies during the recovery period were obtained before consolidation regimen. We used morphometry to calculate the cellularity and myeloid to erythroid ratio and quantified megakaryocytes CD10 versus time from day 14 onward. The absolute neutrophil and platelet counts for 28 cases were related to histologic recovery. Results.—From day 14, we noted a differential slope of recovery of these patients with no difference in male and female patients, P = .45, but a difference between younger and older patients (>58.5 years), P = .03. After regenerative hyperplasia, the cellularity plateaus, the myeloid to erythroid ratio, and the megakaryocytes even out with platelet normalization, and the early CD10+ B cells rise from day 40 onward, P = .01. The patterns of recovery after day 60 of postchemotherapy and posttransplantation patients are similar. Complete histologic and peripheral blood recovery is noted at day 38 and thereafter. Conclusions.—By linear equation using at least 2 trephine biopsy specimens, the projected rate of cellular recovery may be determined, and 5 histologic features are associated with complete histologic recovery.


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.


1993 ◽  
Vol 11 (6) ◽  
pp. 1046-1054 ◽  
Author(s):  
S Amadori ◽  
A M Testi ◽  
M Aricò ◽  
A Comelli ◽  
M Giuliano ◽  
...  

PURPOSE This study was conducted to assess the comparative values of allogeneic bone marrow transplantation (BMT) and autologous bone marrow transplantation (ABMT) with sequential postremission chemotherapy (SPC) in children with acute myelogenous leukemia (AML) in first remission. PATIENTS AND METHODS From March 1987 to March 1990, 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and standard-dose cytarabine. After initial consolidation with a course of daunorubicin, cytarabine, and thioguanine (DAT), patients in complete remission (CR) were randomized to receive either ABMT or SPC, except for those with an HLA-matched sibling who were assigned to undergo BMT. SPC consisted of three additional courses of DAT, followed by three pairs of drugs administered sequentially for a total of six cycles. RESULTS Overall, 127 of 161 patients attained CR (79%). The estimated probabilities of survival and event-free survival (EFS) at 5 years for all patients were 42% and 25%, respectively (median follow-up, 28 months). For the 127 complete responders, the 5-year probability of disease-free survival (DFS) was 31%, with a cumulative risk of relapse of 64%. For the purpose of this study, all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle, regardless of whether they actually received the intended therapy. The 5-year DFS was 51% for the BMT group (n = 24), significantly higher (P = .03) than that observed for the other cohorts: 21% for ABMT (n = 35), 27% for SPC (n = 37), and 34% for a group of 31 nonrandomized (NR) patients. Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups, including the BMT cohort, in which no deaths attributable to the toxicity of the procedure were recorded. CONCLUSION The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission.


1993 ◽  
Vol 11 (2) ◽  
pp. 279-286 ◽  
Author(s):  
U Creutzig ◽  
J Ritter ◽  
M Zimmermann ◽  
G Schellong

PURPOSE One of the goals of study AMA-BFM-87 was to test prospectively in acute myelogenous leukemia (AML) patients if cranial irradiation could be replaced by late intensification therapy with high-dose cytarabine (Ara-C) and etoposide (VP-16). PATIENTS AND METHODS Patients with a low risk of CNS relapses (ie, no initial CNS disease, WBC count at diagnosis < or = 70.000/microL) were randomized for irradiation (group A, 31 patients). In 25 patients (group B), randomization was refused. As interim results showed no increase of CNS relapses in nonirradiated patients, prophylactic irradiation was discontinued after 2 1/2 years to prevent unnecessary CNS toxicity. Forty-four patients (group C) entered the study after randomization had been stopped. RESULTS In all patients with a low risk of CNS recurrences (n = 100), a significantly higher probability of relapse-free interval (pRFI) of 5 years was found in irradiated patients (pRFI = .78) compared with nonirradiated patients (pRFI = .41) (P = .007). Moreover, a slightly higher incidence of CNS relapses was observed in nonirradiated patients. Due to the small number of patients, this was not observed when randomized patients only were analyzed. In accordance with these findings, the favorable outcome of low-risk patients in the preceding study, AML-BFM-83 (pRFI > .80), could only be reproduced in study AML-BFM-87 in patients who had received cranial irradiation. CONCLUSION These results indicate that cranial irradiation should be an integral part of the treatment of all AML patients not undergoing bone marrow transplantation. Residual blasts in the CNS may escape systemic chemotherapy and lead to recurrence of the initial disease not only in the CNS, but also in the bone marrow.


2000 ◽  
Vol 103 (3) ◽  
pp. 125-134 ◽  
Author(s):  
H.M. Schmetzer ◽  
S. Braun ◽  
D. Wiesner ◽  
T. Duell ◽  
H.H. Gerhartz ◽  
...  

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