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Biomedical subjects

M Bonfichi

Publications and source records attributed to M Bonfichi.

At least 37 records · Page 2Linked to original sources

Karyotype in myelodysplastic syndromes: relations to morphology, clinical evolution, and survival.

One hundred eighty-eight unselected consecutive patients with "de novo" myelodysplastic syndrome (MDS) were studied cytogenetically. They were subclassified as 4 refractory anemia with ringed sideroblasts (RARS), 67 refractory anemia (RA), 58 refractory anemia with excess of blasts (RAEB), 40 RAEB in transformation (RAEB-t), and 19 chronic myelomonocytic leukemia (CMML). The overall incidence of chromosome abnormalities was 69%. The RAEB and RAEB-t patients showed karyotypic changes, more often than RA and CMML (76% and 100% vs. 56% and 42%, respectively). The most frequent single anomaly was del(5)(q13-q22q33) (22 cases), followed by monosomy 7 or del 7q (11 cases), del(11) (q14q23) (8 cases), trisomy 8 (4 cases). Complex karyotypes (defined by the presence of three or more structural or numerical abnormalities) were detected in 33 patients. With regard to the FAB classification, del (5)(q13q33) was associated with RA, and complex rearrangements with RAEB and RAEB-t. Leukemic transformation occurred in 66 patients (46%), none with a normal karyotype or del(11)(q14q23) as single abnormality. In patients carrying 5q- alone, acute evolution correlated with proximal breakpoint localization, being found in no case with del(5)(q13q33) but in three out of four cases with del(5)(q22q33). Acute leukemia (AL) progression happened in all cases with complex rearrangements and monosomy 7 or del(7q). Two of the four trisomy eight patients evolved in AL. By using the Cox proportional hazard regression analysis it was demonstrated that the karyotype abnormality was a significant predictor of leukemic transformation (P < 0.001). Patients with abnormal karyotypes without complex abnormalities had a survival (median survival 12 months) shorter than that of cases with only normal metaphases (median 83 months) (P < 0.001); patients with a mixture of normal/abnormal metaphases had a median survival of 31 months. The median survival for complex karyotypes was 7 months. Among cases with single defects, del(5)(q13q33) showed the best survival (64 months), monosomy 7 and del(7q) the worst (7 months) (P < 0.001).

Chromosome Mapping↗

[Intravenous versus inhalation anesthetics in anesthesia for bone marrow harvest for transplantation].

It is well known that nitrous oxide and many volatile anaesthetic drugs possess a certain degree of myelodepressive activity. The authors' aim has been to evaluate the degree of proliferative activity after exposure to forane or propofol. Bone marrow samples have been cultured after general anaesthesia induced and maintained by the same agents; cultures have also been performed after samples exposure to forane and propofol. The results have not shown significative differences in the haemopoietic colonies growth of bone marrow harvested from patients underwent intravenous or inhalatory anaesthesia. In vitro study has shown a significative variation of the colonies growth at the forane higher concentration. Intravenous anaesthetic may be safer for bone marrow harvest for transplantation.

Adolescent↗

Risk assessment in myelodysplastic syndromes: value of clinical, hematologic and bone marrow histologic findings at presentation.

We analyzed the prognostic value of clinical, hematologic and bone marrow (BM) histologic findings at presentation in 94 patients with myelodysplastic syndromes (MDS) (28 RA; 2 RARS; 34 RAEB; 6 CMML; 24 RAEB-t). With survival as the dependent variable, stepwise multivariate analysis indicated as the prognostically most important factors among the MDS taken as a whole: latency from the first symptoms to diagnosis, age, and percentage of BM blasts. In each main MDS group the most unfavorable initial characteristics were: 1) low Hb, no macro-megaloblastosis, male sex for RA/RARS; 2) low Hb and low platelet levels for RAEB/CMML; 3) granuloblastic hyperplasia and high BM blastosis for RAEB-t. Of the BM histologic parameters, only the percentage of blasts had significant prognostic value. Histologic assessment of BM blastosis, however, did not differ statistically from that based on cytologic examination of BM smears, so that marrow histology seemed not essential for initial prognostic assessment in MDS patients. The finding of abnormal localization of immature precursors (ALIP) in BM biopsies was associated with a negative trend without reaching statistical significance. Using four objective parameters of proven significance (age, Hb, platelets, and BM blasts) we devised a staging system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.

Biopsy, Needle↗

Impact of advanced age on the management of acute nonlymphocytic leukemia: a study of 103 patients.

Treatment and outcome of 103 consecutive patients aged greater than or equal to 60 with de novo acute nonlymphocytic leukemia (ANLL) were reviewed. Twenty-three cases (22%) were not suitable for induction chemotherapy because of very poor presenting general conditions and could receive supportive care alone. The majority of them died within 1 month. Twenty-eight patients (27%) aged greater than or equal to 70 and/or with concurrent nonhematologic disorders underwent mild induction chemotherapy, which produced 3 complete remissions. The median survival for this group was 2 months. Only 52 patients (50%) were considered eligible for conventional induction chemotherapy. For this group, response rate was 34.5%, the median survival was 3.5 months, and median survival for responding patients was 13 months. Only intensive chemotherapy seems capable of substantially improving prognosis for older ANLL patients. This approach, however, is feasible only in a minority of patients, due to a high incidence of life-threatening complications.

Age Factors↗

Mitoxantrone and etoposide: an effective regimen for refractory or relapsed acute myelogenous leukemia.

23 adult patients with refractory or relapsed acute myelogenous leukemia (AML) received salvage chemotherapy with mitoxantrone and etoposide. The regimen consisted of mitoxantrone, 10 mg/m2/d by 30-min infusion, and etoposide 100 mg/m2/d by 30-min infusion, given 12 h apart for 5 consecutive d. Of 23 patients treated, 13 met the criteria for highly refractory disease (6 primary resistant; 4 with early relapse during maintenance; 3 relapsed and refractory to reinduction). 10 patients had relapsed off-therapy more than 6 months after achieving first CR. Overall, 14 patients (61%) achieved a complete remission (CR): 6/13 (46%) with refractory AML, and 8/10 (80%) with relapsed AML. 2 patients had a partial remission, 2 died in aplasia, and 5 were nonresponders. In responding patients, the median time for recovery of granulocyte count was 27 d. The most important nonhematologic side effect was oral mucositis, which was severe in 35% of cases. No signs of cardiac toxicity were observed. The median CR duration was 5 months (range, 2 to 12+ months). The combination of mitoxantrone and etoposide appears a highly effective and relatively well tolerated salvage regimen for refractory and relapsed AML. Its incorporation into first-line induction and consolidation programs for newly diagnosed AML patients should be considered.

Adult↗

Acute nonlymphocytic leukemia: evidence of clonogenic cells in peripheral blood in early complete remission.

We describe a patient with acute nonlymphocytic leukemia in whom chromosomal analysis showed a 8,21(q22;q22) translocation and who entered complete remission after one course of chemotherapy. During the post-chemotherapy aplastic phase blood-derived hemopoietic circulating stem cells were collected by continuous flow aphereses. Chromosomal analysis on the collected cells and on colonies (CFU-GM grown in agar) showed the same anomaly as was present at diagnosis in about 30% of those analyzed. This confirms the persistence of the malignant clone in the early phase of the clinical remission in acute nonlymphocytic leukemia.

Adult↗

Prognostic factors in non-Hodgkin's lymphomas.

Prognostic factors were investigated in 67 patients with non-Hodgkin's lymphomas, homogeneously staged and treated (COP or CHOP according to low or high malignant histotype). A large number of parameters were scrutinized in order to recognize those exhibiting a prognostic value regarding length of survival. All the parameters that singly appeared to influence survival were entered into a multiple regression factor analysis. The erythrocyte sedimentation rate (ESR), higher or lower than 35 mm at the 1st h, better discriminated the groups of patients surviving or not at a given time. The histologic type, according to the Kiel classification of malignancy, was the second best prognosticator when a short-term prediction was requested (survival or death after no more than 2.5 years), but showed insufficient statistical weight for predicting longer survivals (greater than 4 years). Stage seemed to be the third best prognosticator for the first years of survival, but only the second best for longer survivals. Other parameters had very low prognostic importance when compared with those above. The results were substantially confirmed by 28 other patients, taken as controls. The importance that such a simple and easy test as ESR may be adequate with regard to prognosis is emphasized.

Adult↗

[Biological screening of immuno-mediated marrow insufficiency by means of the CFU-GM assay].

We studied in agar growth behaviour of bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in 16 patients with marrow failure in order to discriminate patients with cells inhibiting granulopoiesis both in bone marrow and peripheral blood. Our experimental design was based on: a) agar culture of bone marrow cells before and after treatment with antilymphocyte globulin (AGL); b) agar co-culture of marrow cells with autologous lymphocytes from peripheral blood. ALG treatment of marrow cells determined CFU-GM growth increase in 4 out of 10 patients; in the same patients co-culture with autologous lymphocytes showed a significant inhibition of CFU-GM growth. The growth enhancement induced by ALG treatment "in vitro" associated with growth inhibition in the coculture suggests the existence of a lymphocyte population suppressing the granulopoiesis both in bone marrow and peripheral blood. With this work we propose an experimental model in order to discriminate marrow failure based on cell-mediated suppression of CFU-GM growth in patient susceptible of immunosuppressive therapy with ALG.

Adolescent↗