Analysis Of The Blasts In Bone Marrow Trephine Biopsy When Bone Marrow Smear Achieves Complete Remission In Acute Leukemia

Acute leukemia (AL) is a biologically heterogenous diseasecharacterized by a clonal acumualation of immature blood cells, whichultimately leads to bone marrow failure. The management of AL iscomplex and the prognosis of AL has gained great progress. It isreported that the five-year disease-free-survival of adult ALL hasalready achieved 40%, however, the therapy of ANLL is still far fromsatisfaction, with only 30% to 40% of patients treated withchemotherapy are cured. Attaining CR following inductionchemotherapy is also a prerequisite for long-term survival in AL.However, many patients who achieve CR ultimately relapse and diefrom their disease. To date, widely used definitions of CR have beenbased solely on cytologic examination of bone marrow (BM) andblood. However, as the rate of relapse after attaining morphologic CRis high, one could conclude that these criteria for CR lack a sufficientpredictive value for clinical outcome, and cannot be used to stratifypatients into risk-adapted therapeutic subgroups. This problem likelystems from the low sensitivity of morphological examination fordetection of residual disease in remission bone marrow samples.According to the criteria for AL, CR was defined by adequate bonemarrow cellularity (> 20%) with maturation of all cell lineages, lessthan 5% blasts, and no detectable Auer rods, in addition to ≥1,500/μL neutrophil and 100,000/μL platelet counts in the absence ofcirculating blasts. These criteria were based only on morphologicalanalysis. Unfortunately, blasts were found in trephine biopsyspecimens in some patients while the aspiration smears achieved CRcriteria in clinical practice. Past studies showed that the patients whosebiopsy specimens were blasts positive while aspiration smearsachieved CR criteria had a worse response to chemotherapy, a higherrate of recurrence and a shorter overall survival, compared with thepatients whose biopsy specimens had no blasts. To our disappointment,however, the studies mentioned above had not went through statisticalprocess. That is to say, the validity of the conclusion driven from thosestudies were not so convincing. Is there any association between theblasts found in the biopsy specimens when aspiration smears show CRand the prognosis of patients with AL? Do those AL with blasts inbiopsy specimens have unique clinical and laboratory characteristics?How do they respond to chemotherapy? Is the time of bone marrowsurpression in those patients as long as that in other AL patients?Therefore, we conducted a study to investigate the usefulness ofbiopsy analysis as a predictor for clinical outcome. To our knowledge,this is the first relatively large study indicating that the significance ofblasts in the biopsy specimens in AL patients who had receivedmorphologic CR. Of the 109 patients eligible for this study, 22 hadblasts in the biopsy specimens when the aspiration smears showed CR.Of the 22, 16 were ANLL (8 cases of M2,7 cases of M4, 1 case ofM5), and 6 were ALL (4 cases of B-ALL, 1 case of T-ALL, one werenot identified). Of the 22,12 were male and 10 were female. Themedian age of the 22 patients were 38 years old. The average of thecomplete blood count and the percentage of bone marrow blasts atdiagnosis were as followes: white blood cell count 14.4×109/L,hemoglobin72.7g/L,platelet64×109/L,and the bone marrow blasts57.4%. Of the 22, abnormal karyotypes were found in 4 patients: M5,47, XY, +19;M4E0, 45, XY, -18;M4E0, 48,XY, +8, +10, del (16)(q22);M4E0, 46, XX, inv (16) (P13;q22). Compared with the patientswith negative blasts in biopsy specimens, those whose blasts werepositive had a higher percentage of bone marrow blasts at CR, but hadno difference in age, sex, and karyotypes at diagnosis. Our studydemonstrated that the blasts positive group had a shorter OS and DFS,and was easier to relapse,but there were no statistical significancebetween the two groups when referred to OS and DFS. Taken thenumber of sample and the ununiform time of bone marrow examation,the conclusion should be revalued by larger studies. This wasconfirmed by the Cox model analysis of the risk factors of acuteleukemia, which showed that the blasts in bone marrow trephinebiopsy when bone marrow smear achieved complete remission wasthe risk factor of adverse prognosis in acute leukemis.Conclusion: Morphological CR is not the true bone marrow CR,and pathological CR should be considered when evaluating patients'CR with acute leukemia.