Bone marrow morphologic changes after combination chemotherapy including VP-16
✍ Scribed by David J. Adelstein; John D. Hines
- Publisher
- John Wiley and Sons
- Year
- 1985
- Tongue
- English
- Weight
- 399 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0008-543X
No coin nor oath required. For personal study only.
✦ Synopsis
Bone marrow aspirates and biopsy specimens were examined from seven patients with small cell lung cancer. All patients had received recent combination chemotherapy including VP-16. No correlation between marrow biopsy cellularity and hematologic toxicity could be established. However, an unusual combination of morphologic changes was seen. This included an initial rapid increase in the M:E ratio, interference with cell division, and eventual cell death. There was little evidence of mitotic arrest or megaloblastosis. These changes are consistent with the known mechanism of action of VP-16, the only agent given to all patients. The small sample size and the unknown contributions of the other cytotoxic agents administered allow only limited conclusions.
Cancer 56:467-471, 1985.
MALL CELL CARCINOMA aCCOUntS for 20% to 25%
S of all primary lung cancer. It is considered both the most rapidly growing and the most chemotherapysensitive cell type. All patients, irrespective of disease extent, are candidates for chemotherapy at the time of diagnosis, and responses can be expected in up to 90%. Aggressive combination chemotherapy is utilized with regimens containing several of the active single agents such as doxorubicin (Adriamycin), cyclophosphamide, vincristine, VP-16, methotrexate and CCNU.'-3 Early and widespread hematogenous dissemination is another characteristic of small cell lung cancer, and vigorous staging evaluations have been recommended. In view of the fact that up to 45% of patients with this disease will have evidence of bone marrow involvement at the time of presentation, bone marrow examination has been considered a routine staging procedure.'-'
Recently, at our institution, seven patients with rapid disease growth and serious impending complications, were given chemotherapy immediately after diagnosis and before the completion of staging. This has provided us with the unusual opportunity to examine the bone marrow of patients shortly after having received combination chemotherapy with a regimen containing VP-16. The striking morphologic changes observed have prompted this review.
Materials and Methods
Between 1 and 5 days after the initiation of combination chemotherapy, a bone marrow aspirate and biopsy was performed using standard technique in the posterior iliac crest. Wright's stained cover slips of bone marrow aspirate spicules were reviewed independently by both authors and a 500 nucleated cell differential was performed by one (D.J.A.). The myeloid/erythroid (M:E) ratio was determined and the number of mitotic figures expressed per 500 cells. Morphologic changes were either present (+), extensive (++) or not seen (-). Changes were considered extensive if present in more than 25% of the elements of the appropriate marrow cell line.
Bone marrow biopsy specimens were reviewed, after routine hematoxylin and eosin (H & E) staining, for an estimate of the percentage cellularity, and for the presence of metastatic tumor. Pretreatment and nadir blood counts were recorded. Additionally, Wright's stained peripheral blood smears were examined for evidence of megaloblastosis.
Results