The Criteria for Bone Marrow Recovery Post–Myelosuppressive Therapy for Acute Myelogenous Leukemia: A Quantitative Study

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.

Download Full-text

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

Transplantation in Hematology and Oncology ◽

10.1007/978-3-642-59592-9_14 ◽

2000 ◽

pp. 130-133

Author(s):

K. Kratz-Albers ◽

J. Kienast ◽

H. Ostermann ◽

R. Leo ◽

Th. Büchner ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Peripheral Blood ◽

Acute Myelogenous Leukemia ◽

Myelogenous Leukemia ◽

Acute Myelogenous

Download Full-text

Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.6.1046 ◽

1993 ◽

Vol 11 (6) ◽

pp. 1046-1054 ◽

Cited By ~ 108

Author(s):

S Amadori ◽

A M Testi ◽

M Aricò ◽

A Comelli ◽

M Giuliano ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Acute Myelogenous Leukemia ◽

Marrow Transplantation ◽

Autologous Bone Marrow Transplantation ◽

Myelogenous Leukemia ◽

Allogeneic Bone ◽

Free Survival ◽

Acute Myelogenous ◽

First Remission

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.

Download Full-text

The Study of the Expression of TNF in Bone Marrow Specimens and Survival in Patients with Acute Myelogenous Leukemia.

Blood ◽

10.1182/blood.v108.11.4415.4415 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4415-4415

Author(s):

Merrill K. Shum ◽

Karine Hageboutros ◽

Ziad Skaff ◽

Shoba Kankipati ◽

Alexandre Hageboutros

Keyword(s):

Bone Marrow ◽

Acute Myelogenous Leukemia ◽

Clinical Remission ◽

Prospective Trial ◽

Small Sample ◽

Myelogenous Leukemia ◽

Chi Square ◽

Bone Marrow Biopsies ◽

Tnf Α ◽

Acute Myelogenous

Abstract Background: The objective of the current study was to assess the correlation between the expression of TNF from bone marrow specimens and survival in patients with acute myelogenous leukemia (AML). Methods: Immunohistochemical analysis of bone marrow biopsies from 10 patients recently diagnosed with AML was performed using the dakocytomation LSAB + system -HRP kit, to stain for TNF binding. TNF-α and TNF-β expression were analyzed for color intensity and assigned a score from (0–5+) with 5+ being bright and over-expressed. Results: Bone marrow specimens from 4 women and 6 men (n=10), median age 34 (range 19–61 years), all diagnosed with AML, revealed high TNF-β expression (3, 4, 5+) in 8/10 patients and high TNF-α expression (3, 4, 5+) in 6/10 patients. Median survival was 5.5 (range 1–54 months). Fisher’s exact tests for paired samples showed no correlation between predictors (age, sex, survival) and outcomes (TNF-α, TNF-β). Pearson Chi-square tests showed no correlation between predictors (age, sex, survival) and outcomes (high TNF-α / high TNF-β expression, mixed TNF-α /TNF-β expression, low TNF-α / low TNF-β expression) [See chart below]. However there was an association seen with younger males expressing both high TNF-α and high TNF-β and older women expressing low TNF-α and low TNF-β. Interestingly, the eldest patient who expressed TNF-β 4+ and TNF-α 3+ also survived the longest. He achieved clinical remission after standard induction chemotherapy, but relapsed 8 times over a course of 54 months. During each clinical remission, the patient was treated with infliximab (a TNF-α blocker) for his Crohn’s disease. Conclusion: Level of expression of TNF-α and TNF-β of bone marrow biopsies from our AML patients showed no correlation with age, sex or overall survival given the small sample size. A large, prospective trial will be needed to determine the significance of TNF-α or TNF-β expression with survival and whether TNF-α blockade alone or in combination with chemotherapy plays a role in the treatment of patients with AML over-expressing TNF-α. SUMMARY OF ASSOCIATIONS OUTCOMES TNF α+TNFβ* TNF α** TNF β** *Pearson Chi-square with 2dF **Fisher’s Exact Test Sex 0.43 0.57 0.47 PREDICTORS Survival 1.00 1.00 1.00 Age 0.26 0.52 0.42

Download Full-text