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H Tilly

Publications and source records attributed to H Tilly.

At least 19 recordsLinked to original sources
PubMed1992

All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases.

We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course ("4 + 7" course), then three "2 + 5" DNR + Ara C courses and maintenance chemotheapy. However, the "4 + 7" course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the "4 + 7" course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the "4 + 7" course. Four patients did not receive this course but received the subsequent "2 + 5" courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1992

Translocations involving band 3q27 and Ig gene regions in non-Hodgkin's lymphoma.

We report a series of 20 non-Hodgkin's lymphomas (NHL) in which cytogenetic analysis showed a translocation involving band 3q27 and the site of one of the three Ig genes (14q32, 2p12, 22q11) in the neoplastic cells. These cases were found in a series of 319 patients with clonal chromosomal abnormalities studied over a 7-year period. Fourteen patients had diffuse lymphoma, mainly of large cell type and the remaining six were follicular lymphomas. All cases studied were of B-cell phenotype. A t(3;14)(q27;q32) was commonest, found in 15 patients (4.7%), with the two variant translocations, t(3;22)(q27;q11) and t(2;3)(p12;q27), being found in three and two patients, respectively. Additional chromosomal defects were present in most patients, but two patients had this type of translocation as the sole abnormality. These results indicate that translocations involving band 3q27 and Ig genes are not uncommon, and suggest that a novel oncogene, located at band 3q27, may be implicated in B-cell NHL.

Adult↗
PubMed1992

Immunological evaluation of harvested stem cells obtained by leukapheresis after chemotherapy.

Some patients suffering from malignancies may benefit of myeloablative chemotherapy followed by hematological reconstitution with autologous peripheral blood reinfusion. A quick evaluation of the number of hematopoietic progenitors present in leukapheresis blood samples is necessary to ensure the collection of a sufficient number of these cells. A study was performed on a series of 25 leukapheresis following initial chemotherapy. The number of granulomonocytic colony-forming unit (CFU-GM) and the number of CD34+ cells were evaluated simultaneously, in each sample. Results have shown a relatively strong linear correlation between both methods of evaluation of hematopoietic progenitors, suggesting that immunophenotyping could be a useful method to estimate the number of progenitors.

Adult↗
PubMed1992

Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients treated with the LNH-84 regimen.

PURPOSE: Of the 737 patients with aggressive lymphoma who were treated with the LNH-84 regimen, 244 with progressive disease after complete remission or partial response were analyzed retrospectively to determine the influence of intensive chemotherapy with bone marrow transplantation (BMT) on survival. PATIENTS AND METHODS: Forty-four patients were treated with salvage chemotherapy, followed by autologous bone marrow transplantation (ABMT) in 40 and allogeneic BMT in four. The other 200 patients were treated with chemotherapy only. RESULTS: Salvage treatment produced an objective response in 57% of the patients; 23% achieved a second complete remission. Median overall survival was longer for patients who were treated with ABMT than for those who were treated with chemotherapy only (12.4 v 6.7 months), as was median freedom from progression (FFP) survival (7.7 v 4 months). In multiparametric analysis, ABMT and normal initial lactic dehydrogenase (LDH) level were the primary parameters associated with longer survival. This is also true when (1) only patients younger than 60 years of age, (2) only patients who responded to salvage regimen, or (3) only patients with both conditions were included in the analysis. Patients who were not transplanted had a 1.69 to 2.26 relative risk of dying from their disease compared with those who were treated with intensive chemotherapy plus ABMT. CONCLUSION: This study produced more evidence of the favorable impact of intensive chemotherapy with bone marrow rescue on survival in lymphoma patients who had relapsed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Production of hyaluronan-binding glycoprotein by human monocytes. Its use as marker in myeloid leukemia].

A hyaluronan-binding protein fraction was isolated by affinity chromatography of peripheral human blood mononuclear cell culture medium through immobilized hyaluronan. The presence of a hyaluronan-binding protein similar to human brain hyaluronectin was demonstrated by (i) the ELISA method on hyaluronan-coated plastic plates using anti-hyaluronectin antibodies, (ii) the lowering of the elution volume of the protein on liquid gel chromatography in the presence of hyaluronan, (iii) the extinction of the reaction to human brain hyaluronectin when antibodies were absorbed out with monocyte hyaluronectin, (iv) western blotting with polyclonal and monoclonal anti-hyaluronectin antibodies. The hyaluronectin-producing cells were adherent (10 min., 37 degrees C) to plastic, esterase (+) and CD 14 (+) cells and had the morphology of monocytes. The protein expression was investigated in leukemic cells by means of the immunocytochemical method. Hyaluronectin expression was restricted to 4/12 of M4 and M5 types of acute myeloid leukemias. Other myeloid leukemia and acute lymphoblastic leukemia cells were negative. The results indicate that hyaluronectin can be produced under free form in the absence of hyaluronan, by human peripheral blood monocytes. It supports the hypothesis that the expression of hyaluronectin in tumour stroma could be due, at least in part, to inflammatory cells of the tumour. The expression of the protein by M4 and M5 acute myeloid leukemia cells suggests that hyaluronectin could be synthesized by immature cells of the monocytic lineage as well as by mature monocytes.

Biomarkers, Tumor↗
PubMed1991

Cytogenetic studies in untreated Hodgkin's disease.

Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11-13, 13p11-13, 3q26-28, 6q15-16, and 7q31-35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11-13 (P less than .01), 13p11-13 (P less than .01), 14p11 (P less than .01), 15p11-13 (P less than .02), and 20q12-13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12-13 (P less than .01) and 13p11-13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.

Adolescent↗
PubMed1991

Aggressive primary gastrointestinal lymphomas: review of 91 patients treated with the LNH-84 regimen. A study of the Groupe d'Etude des Lymphomes Agressifs.

PURPOSE: Patients with aggressive primary gastrointestinal lymphoma undergoing the LNH-84 chemotherapy regimen were analyzed to determine the efficacy of intensive combination chemotherapy, the role of surgical debulking in patients treated with combination chemotherapy, and the toxicity associated with each of these modalities. PATIENTS AND METHODS: Ninety-one patients with primary gastrointestinal lymphoma who participated in the prospective multicenter LNH-84 combination chemotherapy trial (total number of patients in trial, 737) were analyzed. These 91 patients included 69 (76%) with diffuse large cell, nine (10%) with diffuse mixed, and seven (8%) with small noncleaved cell lymphoma. Two patients (2%) had stage IE, 54 patients (59%) stage IIE, and 35 patients (38%) stage IV disease; all patients with stage IE, 22 with stage IIE, and 18 with stage IV disease had bulky (greater than or equal to 10 cm) tumors. Specific sites of gastrointestinal involvement included stomach (47%), small bowel (38%), ileocecum (14%), colon (11%), and rectum (7%). Although surgical resection was attempted in 71 patients (78%), only 28 (31%) had complete tumor excision. All patients received three or four cycles of ACVB (defined in text) induction therapy followed by sequential consolidation as previously described. RESULTS: Responses to treatment in the 91 patients included 71 (78%) complete remissions, six (7%) partial remissions, five (5%) nonresponses, and nine (10%) deaths. With a median follow-up of 3 years, 10 patients (14%) have had relapses; predicted 4-year disease-free survival of complete responders is 85% and predicted 4-year survival of the entire group is 62%. In patients with stage IE or IIE disease, the complete response, survival, and disease-free survival rates were similar in those who underwent complete surgical resection or incomplete or no surgical resection prior to the administration of combination chemotherapy. Prognostic factors predicting for survival in the 91 patients with primary gastrointestinal lymphoma were similar to those in the 646 other patients treated with the LNH-84 regimen. CONCLUSIONS: Patients with aggressive gastrointestinal lymphoma treated with intensive chemotherapy have outcomes and prognostic factors comparable to those of patients with similar-stage aggressive lymphoma without primary gastrointestinal involvement. Surgical resection prior to the administration of combination chemotherapy did not influence the complete response rate, survival rate, or disease-free survival rate in this small group of patients.

Adolescent↗
PubMed1991

HIV-associated non-Hodgkin's lymphomas: clinical characteristics and outcome. The experience of the French Registry of HIV-associated tumors.

From 1/87 to 12/89, the French Registry of HIV-associated tumors recorded 131 cases of intermediate- and high-grade non-Hodgkin's lymphomas (NHL). There were 47 small non-cleaved Burkitt-type lymphomas (SNCL), 32 immunoblastic lymphomas (IL) and 52 diffuse large-cell or predominantly large-cell lymphomas (LCL). There were differences in the clinical patterns of the histological subtypes. Isolated extranodal presentation was less frequent in SNCL (2/47) than in IL (13/32) and LCL (17/49) (p less than 0.0001). In the latter two groups, the central nervous system was the principal site of extranodal involvement (16/30), 87% of SNCL, patients had no previous manifestations of AIDS whereas 40% of IL and LCL patients presented full-blown AIDS (p less than 0.01). At the time of NHL diagnosis, the median blood CD4 lymphocyte count was higher in SNCL (266/microL) than in LCL (125/microL, p less than 0.05) and IL (80/microL, p less than 0.01), 69% of stages I/II patients, 31% of stages III/IV, and 33% of stage ie patients achieved complete remission (CR), p less than 0.05. Overall median survival time was 5 months. There was no statistical difference in CR and survival rates among histological types. The two-year actuarial survival rate was 25% (median 8 months) for initially asymptomatic patients or those with persistent generalized lymphadenopathy (PGL) and 9% (median 3 months) for those previously with AIDS-related complex (ARC) and AIDS patients (p less than 0.001). Response to treatment was the other predictor factor. The two-year survival rate was 42% (median 16 months) for patients who achieved CR, and 5% (median 3 months) for those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Prognostic factors in aggressive malignant lymphomas: description and validation of a prognostic index that could identify patients requiring a more intensive therapy. The Groupe d'Etudes des Lymphomes Agressifs.

The objectives of this study were to determine prognostic factors for response to treatment, freedom-from-relapse (FFR) survival, and overall survival of 737 aggressive malignant lymphoma patients treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, methotrexate with leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH-84) regimen; to construct a prognostic index with factors isolated by multivariate analyses; and to validate this prognostic index with another set of patients. Complete response (CR) was reached in 75% of LNH-84 patients, and 30% of them relapsed. With a median follow-up of 36 months, median FFR survival and median overall survival were not reached. Low serum albumin level, high tumoral mass, weight loss, bone marrow involvement, greater than or equal to 2 extranodal sites, and increased lactic dehydrogenase (LDH) level were associated with a low response rate. Advanced stage, increased LDH level, and nonlarge-cell histologic subtypes (diffuse mixed, lymphoblastic, and small non-cleaved) were statistically associated with a high relapse rate and short FFR survival. Increased LDH level, low serum albumin level, tumoral mass larger than 10 cm, greater than or equal to 2 extranodal sites, advanced stage, and age older than 65 years were statistically associated with short overall survival. Four of these parameters, namely, LDH level, stage, number of extranodal sites, and tumoral mass, were put together to construct a prognostic index. This index partitioned LNH-84 patients into three subgroups of good, intermediate, and poor prognosis (P less than .00001): CR rates of 93%, 83%, and 61%; relapse rates of 12%, 25%, and 45%; 3-year FFR survival of 87%, 73%, and 53%, and 3-year survival of 88%, 71%, and 41%, respectively. This prognostic index was applied to a test set of patients: 155 patients treated on protocols of the Nebraska Lymphoma Study Group. Using this index, these patients had 3-year FFR survival of 70%, 40%, and 22% (P = .0002) and 3-year survival of 79%, 52%, and 31% (P = .005). In patients with aggressive lymphomas, this simple prognostic index could distinguish between patients requiring intensive treatment such as autologous bone marrow transplantation in first complete remission and those who could be treated with standard regimens.

Adolescent↗
PubMed1991

A randomized trial of amsacrine and rubidazone in 39 patients with acute promyelocytic leukemia.

Thirty-nine patients with untreated acute promyelocytic leukemia (APL) were randomly allocated to receive rubidazone (zorubicin) 200 mg/m2/d, days 1 to 4 plus cytarabine (Ara C) 200 mg/m2/d, days 1 to 7 (arm A, 21 patients), or amsacrine (Amsa) 150 mg/m2/d, days 1 to 4 plus Ara C 200 mg/m2/d, days 1 to 7 (arm B, 18 patients). Prophylaxis of disseminated intravascular coagulation was made by platelet transfusions and heparin. In case of leukemic resistance, patients received a second course with 2 days of rubidazone (arm A) or Amsa (arm B) and 3 days of Ara C. Patients who achieved complete remission (CR) received three consolidation courses with the two drugs used for induction and maintenance therapy for 3 years. Two patients in arm A and one in arm B were allografted in first CR. Initial characteristics were similar in both arms. In arm A, 18 patients (86%) reached CR, two had hypoplastic death, and one had leukemic resistance after two courses. In arm B, 12 patients (66%) achieved CR, two had early death (CNS bleeding, one case; ventricular fibrillation, one case), and four had resistant leukemia after two courses. The difference in CR rate between the two arms was not significant. In arm A, disease-free survival (DFS) showed a plateau at 54.3% after 34 months (95% confidence interval [CI], 32.1% to 74.9%), with eight CRs longer than 34 months. In arm B, DFS was significantly shorter (P less than .03), showing a plateau at 16.7% after 38 months (95% confidence interval, 4.7% to 44.6%), and only two prolonged CRs were seen. The difference in DFS remained significant after censoring allografted patients and patients who died in CR (one in arm A, two in arm B). Our results suggest that Amsa-Ara C combinations may be inferior to anthracycline-Ara C combinations in the treatment of APL, because they seem to provide shorter DFS and, possibly, a higher incidence of initial leukemic resistance. However, studies with larger numbers of patients are required.

Adolescent↗
PubMed1991

Rearrangements of immunoglobulin light and heavy chain genes and correlation with phenotypic markers in B-cell chronic lymphocytic leukemia.

Twenty-five patients with B-cell chronic lymphocytic leukemia (B-CLL) were investigated to correlate the immunological phenotype with the description of the Ig gene rearrangements of the B-cell clone. All patients were positive for the CD19 antigen and one pan B-antigen, markers of late cells (CD20, CD37 or Y2955). Twenty-four of the 25 patients tested expressed monoclonal cell surface immunoglobulin (SIg). The CD5 antigen was present in 21 of the 25 tested patients. Immunoglobulin gene rearrangements were detected by hybridization of the BamHI, EcoRI, BgIII, and HindIII digested genomic DNAs to the IGHJ, IGKC, IGLC, and IGLJ2 probes. Twenty-four of 25 patients had two rearranged IGH loci. The IGKC rearrangements were observed in 20 patients. In four patients, the IGK loci were deleted on both chromosomes. One patient without SIg displayed a germline pattern. All six patients with lambda producing B-CLL showed a lambda gene rearranged band, although the use of IGL polymorphism to investigate IGL rearrangements must be noted. These clonal rearrangements of IGL genes, together with the detection of either the kappa or lambda light chain of SIg, confirm that patients with B-CLL meet the developmental scheme of ordered light chain gene rearrangements.

B-Lymphocytes↗
PubMed1990

Effect of chemotherapy on resting energy expenditure in patients with non-Hodgkin's lymphoma. Results of a sequential study.

This study compared the resting energy expenditure (REE) modifications observed during successive intensive identical chemotherapy courses in non-Hodgkin's lymphoma patients to assess indirectly the metabolic changes induced by the cytotoxic effect of drugs on the tumor. With this therapeutic regimen, reduction of tumor mass is mostly achieved during the first course of chemotherapy. The study included 10 non-Hodgkin's lymphoma adult patients receiving three intensive 5-day courses of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vindesine, and bleomycin. Resting energy expenditure was evaluated by indirect calorimetry during each course, first within the first 2 days before chemotherapy and then on days 2, 3 and 5. Initial REE (day 0) on entry into the study (21.8 +/- 1.2 kcal/kg.d-1) represented 99 +/- 6.7% of theoretical REE. Resting energy expenditure on day 0 was lower during course 2 and 3 (19.1 +/- 0.7 and 18.4 +/- 1.8 kcal/kg/d) than during course 1 (21.8 +/- 1.2 kcal/kg/d). The REE profile was different among the 3 courses: course 1 induced a significant REE decrease on days 3 and 5 (P less than 0.01); during course 2, REE remained stable and was lower than during course 1; during course 3, REE increased on days 2, 3, and 5 (P less than 0.05). Energy balance was positive during the three courses and nutritional status remained stable. The REE decrease observed during course 1 may be regarded as the metabolic effect of chemotherapy on the tumor metabolism.

Adult↗
PubMed1990

Cyclosporin for treatment of life-threatening alloimmunization.

We describe a 16-year-old girl with aplastic anemia who, 1 year after initial diagnosis developed a refractory state to platelet transfusions due to alloimmunization and resulting in severe bleeding. Treatment with cyclosporin, initially prescribed as treatment of the bone marrow failure, resulted in prompt decrease in lymphocytotoxic antibodies, which paralleled a marked improvement in platelet recovery. To our knowledge, such a dramatic effect of cyclosporin on alloimmunization has not been previously reported and merits further attention.

Adolescent↗
PubMed1990

CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35.

A chromosomal translocation involving a breakpoint on the long arm of chromosome 5 at position q35 has been reported previously in 17 cases of neoplasia. In 14 of these cases the translocation involves exchange of material between chromosome 2 p23 and chromosome 5. Most cases had been diagnosed histologically as malignant histiocytosis but it was suggested recently, following the study of three cases in one of the author's laboratories, that such tumours are in reality lymphoid tumours. In the present paper we report on 12 further neoplasms with a translocation involving the 5q35 breakpoint and show that all were large cell lymphomas expressing the CD30 (Ki-1) antigen, often classifiable histologically as 'Ki-1 lymphoma'. In five cases there was evidence, based on antigen expression and/or genotypic studies, that the neoplasm was of T lymphoid derivation. These findings provide further evidence that translocations involving 5q35 are associated not with histiocytic malignancy, but with large cell lymphoid neoplasms, including typical cases of 'Ki-1 lymphoma' or 'anaplastic large cell lymphoma'. Since cell lines have been established from five of these cases it may be possible in the future to clone the breakpoint on chromosome 5 and to investigate whether there is a gene in its vicinity with oncogenic potential.

Adult↗