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Biomedical subjects

M Hayat

Publications and source records attributed to M Hayat.

At least 37 records · Page 2Linked to original sources

High incidence of secondary myelodysplastic syndromes following PROMACE-MOPP and involved field radiotherapy for localized gastric non-Hodgkin's lymphomas.

The incidence of secondary myelodysplastic syndromes (MDS) are rarely reported in an homogeneous patient population treated for non-Hodgkin's lymphoma (NHL). Less than 10 per cent of secondary MDS are usually observed in patients treated for Hodgkin's disease and NHL. Data on the incidence of secondary MDS induced by modern chemotherapeutic regimens is needed. Between January 1985 and January 1989, 20 patients with localized gastric non-Hodgkin's lymphomas (stage I to IIE) were prospectively treated at the Institut Gustave-Roussy with PROMACE-MOPP multi-agent chemotherapy and involved-field irradiation. The mean age was 54 years (range 23 to 69 years). Seven patients died while on therapy or relapsed 2 to 28 months after therapy. Thirteen patients were followed up for at least 5 years. Three of the 13 long-term survivors (23 per cent) developed a myelodysplastic syndrome (MDS) 48, 62 and 72 months after the end of therapy. Cytogenetic analysis was performed in two cases and showed-7 and 18q- in one case, t(9;21)(q13;q22), 21q+, i17q in the other case. PROMACE-MOPP plus radiotherapy should not be recommended in patients with localized gastric non-Hodgkin's lymphoma due to the high risk of developing secondary myelodysplastic syndromes.

Adult↗

Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: a phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group.

Twenty-one patients with acute myeloid leukemia (AML) who failed to enter complete remission (CR) after first-line standard-dose remission-induction therapy with 7 days of cytarabine and 3 days of daunorubicin were treated with a salvage regimen containing intermediate-dose cytosine arabinoside (Ara-C) 2 x 500 mg/m2/day during 7 days in combination with continuous infusions of idarubicin 12 mg/m2/day on days 1, 3, and 5. Twenty patients were considered primary resistant, and one patient had a partial remission after two remission-induction courses. Overall, 11 patients (52%, 95% confidence interval: 30-74%) entered CR. Three patients died during hypoplasia and seven patients had resistant disease or a partial remission. The remission rate in this study compares favorably with the results obtained in similar patient categories. The toxicity of this salvage regimen was remarkably mild. No extramedullary toxicity was observed except for hepatic dysfunction in seven patients. The median duration of remission was 8.5 months, and ultimately, all complete remitters have relapsed except the patient who died from infectious complications after allogeneic bone marrow transplantation (BMT). This study shows that new intensive chemotherapy regimens may be effective after failure of primary treatment. Salvage regimens containing intermediate/high-dose Ara-C and/or alternative anthracyclines or anthracenes should be induced in the treatment of young patients with de novo AML.

Adolescent↗

Alternating chemotherapy and radiotherapy for limited-stage intermediate and high-grade non-Hodgkin's lymphomas: long-term results for 96 patients with tumors > 5 cm.

BACKGROUND: The role and timing of radiotherapy for optimal treatment of localized aggressive non-Hodgkin's lymphoma (NHL) is controversial. We report the long-term results of a single-institution pilot study of alternating chemotherapy (CT) and radiotherapy (RT) in patients with clinical stages I or II tumors exceeding 5 cm. PATIENTS AND METHODS: From 1981 to 1992, 96 patients with stages I-II aggressive NHL received an alternating regimen of CT and RT consisting of 8 cycles of CT with 3 courses of RT interjected after the 2nd, 3rd and 4th cycles of CT. The CT combined cyclophosphamide, doxorubicin, teniposide and prednisone every 28 days. Each RT course was started 8 to 10 days after CT (15 Gy in 6 fractions to initially involved and contiguous areas). RESULTS: The median age was 54 years. The disease predominantly located in the head and neck area was stage II in 63% of patients. Bulky tumors (10 cm or larger) were found in 24% of patients. Six patients discontinued CT because of acute toxicity (mucositis). The mean relative dose intensity achieved for doxorubicin, cyclophosphamide and teniposide were 72%, 82%, and 78%, respectively. Late toxicity consisted mostly of severe xerostomia lasting more than 2 years in 7 patients irradiated in Waldeyer's ring. The complete response (CR) rate was 91%; 20 of the 86 patients in CR relapsed (3 locally only). The median follow-up was 61 months, and at 5 years, overall survival (OS) was 77%. Classification according to the International Prognostic Factor Index was possible for 54 patients, all but three of whom were in the 'low risk' group (0-1 factor). Bulky disease was the only unfavorable prognostic factor (P < 0.001) for CR, freedom from progression (FFP) and OS rates; the low relative dose intensity of CT achieved in this study did not affect outcome. CONCLUSION: Alternating chemo-radiotherapy for localized aggressive NHL was feasible and yielded long-term results comparable to those obtained with standard treatments, despite a reduction in dose intensity considerably below that of CHOP which suggested synergistic effects of CT and RT in this scheme.

Adolescent↗

Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group.

PURPOSE: To assess the value of granulocyte-macrophage colony-stimulating factor (GM-CSF) for induction treatment of acute myeloid leukemia (AML), both for priming of leukemic cells and for acceleration of hematopoietic recovery. PATIENTS AND METHODS: GM-CSF was administered 5 micrograms/kg/d by continuous intravenous (i.v.) infusion during induction therapy with daunorubicin (DNR) (days 1 to 3) and cytarabine (ARA-C) (days 1 to 7). A total of 102 patients were randomized onto four arms, as follows: (1) GM-CSF 24 hours before and during chemotherapy (arm +/-); (2) GM-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes (PMNs) (arm -/+);(3) GM-CSF before, during, and after chemotherapy (arm +/+); or (4) no GM-CSF (arm -/-). Stopping rules were applied in case of an initial WBC count greater than 30 x 10(9)/L or a secondary increase of circulating blast cells. Analyses were performed according to the intention-to-treat principle. RESULTS: The complete remission (CR) rates were 77% (arm -/-), 72% (arm +/-), 48% (arm -/+), and 46% (arm +/+). Patients randomized to receive GM-CSF after induction (arms -/+ and +/+) had a significantly lower CR rate (P = .008) and a trend toward accelerated recovery of neutrophils, but no fewer infections or induction deaths. The lower CR rate appeared to be related to an increased resistance rate, with persistent leukemia. The main side effects of GM-CSF were fluid retention and hypotension. CONCLUSION: GM-CSF administered during induction treatment of AML with a DNR/Ara-C combination did not provide any clinical benefit. Furthermore, there was a significant decrease in the CR rate with more persistent leukemia when GM-CSF was administered during the hypoplastic phase after the chemotherapy courses.

Adolescent↗

Interleukin-3 plus low-dose cytosine arabinoside for advanced myelodysplasia: a pilot study. EORTC Leukemia Group.

In an attempt to reestablish normal hematopoiesis in symptomatic myelodysplasia (MDS) and to show the tolerability of a combination treatment of low-dose cytosine arabinoside (LD AraC) and interleukin-3 (IL-3), we treated 31 patients (pts., median age 65 years) who had more than 10% blasts in the bone marrow (BM) and hematopoietic failure with LD AraC (2 x 10 mg/m2 sc, day 1-14) plus IL-3 (once daily sc, day 8-21) at different dose steps (1.0, 2.5, 5.0, and 10.0 micrograms/kilogram body weight). The numbers of each 21-day cycle varied between 1 (3 pts.), 2 (6 pts.), 3 (8 pts.), 4 (1 pt.), 5 (5 pts.), and 6 (8 pts.), in total 116 cycles on an outpatient basis. Subjective tolerability was good in 20 cases (65%). Toxicities were fever (29 pts.), flu-like symptoms (17 pts.), infections (15 pts.), hepatic toxicity (10 pts.), and skin reactions (8 pts.). Overall response was seen in 13 cases (42%) and 5 complete responses (CR), while 10 pts. had stable disease (SD), 5 progressed (2 to acute leukemia), 2 were considered toxic deaths, and 1 died due to the disease. Median survival is 18 months, progression-free survival is 12.5 months (18.0 months in responding pts.), with an actuarial follow-up of 31 months. The data from this phase I/II study show that a combination of LD-AraC and IL-3 is well tolerated and that stable responses can be achieved in MDS by means of an easy outpatient therapy.

Adult↗

Serum interleukin-12 levels in patients undergoing allogeneic or autologous bone marrow transplantation.

Cytokines may be helpful in promoting hematopoietic reconstitution but have also an impact on the cellular interactions that contribute to GvHD and immunologic graft rejection. Because IL-12 is emerging as a central cytokine in immune response, we have investigated its levels in serum samples of patients undergoing bone marrow transplantation and transplant-related events. A double-antibody radioimmunoassay method for monitoring levels of endogenous IL-12, before and after allogeneic (27 patients) or autologous (19 patients) bone marrow transplantation, was used. The serum levels of IL-12 after allogeneic BMT were found to be relatively low (140-300 pg/ml) and similar to the IL-12 levels in the healthy donors (183 pg/ml). Seric IL-12 levels following autologous BMT (350 pg/ml) were higher than those observed in patients receiving an allogeneic BMT and in healthy donors. Our data indicate that the occurrence of GvHD and the development of infection after allogeneic BMT are not associated with IL-12 induction which suggests a possible down-regulation due to immunosuppressive treatment.

Adolescent↗

Can clinical data help to screen patients with lymphoma for MR imaging of bone marrow?

BACKGROUND: Previous studies have suggested combining magnetic resonance (MR) imaging and biopsy in patients with lymphoma but association between MR results and clinical symptoms have never been investigated. The purpose of this retrospective study was to better delineate patients profiles requiring bone marrow (BM) imaging in lymphoma. MATERIAL AND METHODS: 50 MR studies and blind biopsies (BB) were reviewed in 40 patients with lymphoma. MR results were compared to clinical, laboratory-based and BM follow-up data to determine potential associations between MR results and these parameters. RESULTS: 46% of MR studies were abnormal with a normal BB; 2% were normal with an abnormal BB. Abnormal MR results were significantly associated with subsequent bone marrow involvement (p < 0.01). Abnormal MR studies were significantly associated with constitutional symptoms, bone pains (p < 0.05) and an elevated alkaline phosphatase level (p < 0.01). MR imaging excluded malignancy in three patients and caused therapy to be modified in three. CONCLUSION: Abnormal clinical and laboratory-based data should be used to screen patients with normal BB for MR imaging, especially in patients with Hodgkin's disease and high grade non-Hodgkin's lymphoma.

Adolescent↗

Successful chemotherapy including epirubicin in a pregnant non-Hodgkin's lymphoma patient.

We report a case of non-Hodgkin's lymphoma (NHL) successfully treated with combination chemotherapy during pregnancy. The histological diagnosis was large-cell B-type NHL. Four courses of chemotherapy with epirubicin, vincristine and prednisolone were given before delivery. The patient is in complete remission and her baby, now four years old, has developed normally. To our knowledge, this is the first reported case of epirubicin administration during pregnancy and in which chemotherapy was given safely to NHL patients during the second and third trimester of pregnancy.

Adult↗

Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG).

We conducted a prospective, multicenter pilot study of remission induction therapy in patients with poor prognosis MDS and AML evolving from a preceding phase of MDS. Fifty evaluable patients from 15 institutions were treated with one or two remission-induction courses consisting of i.v. idarubicin 12 mg/m2/day on days 1, 2, and 3 combined with a continuous i.v. infusion of cytarabine of 200 mg/m2/day on days 1 to 7. Of the 27 complete remitters (54%), 23 received a consolidation course which was identical to the remission-induction course except for the idarubicin 12 mg/m2 which was given on day 1 only. Fifteen patients received maintenance therapy consisting of six courses of cytarabine 10 mg/m2, s.c. twice daily, for 14 days. Two complete remitters were allografted and five patients received an ABMT. The median survival of all 50 treated patients was 14 months. The median duration of disease-free survival was 11 months with two patients in CR more than 2 years after entering CR. Twenty-four of the 27 remitters have relapsed. Four patients died during remission-induction therapy, but no patient died as a result of persisting hypoplasia. No fatal complications occurred during the consolidation and maintenance courses. Age and stage of disease had no significant impact on CR rate nor on remission duration. The CR rate was significantly (P = 0.03) higher in patients with only normal metaphases compared to patients with cytogenetic abnormalities. The DFS at 2 years was 33 vs 8%, respectively, for patients without or with cytogenetic abnormalities (P = 0.02). This study shows that patients below the age of 60 years with poor risk features are candidates for treatment with combination chemotherapy. A complete remission rate of more than 50% may be expected. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT may be treated with intensive post-remission chemotherapy or autologous BMT.

Adolescent↗

Localized stage non-Hodgkin's lymphoma of the testis: a retrospective study of 16 cases.

The present report concerns a retrospective study of 16 patients with localized intermediate- or high-grade non-Hodgkin's lymphoma of the testis treated in one institution from 1973 to 1990. Ann Arbor stage of disease was IE in 11 and IIE in 5 cases. All except one patient underwent initial inguinal orchidectomy, 11 were disease free after surgery and 12 received inverted Y radiation therapy. All patients achieved a complete remission (CR). Relapse occurred in 8 of 9 patients who did not receive initial chemotherapy, but in only 3 of 7 patients initially treated with chemotherapy including anthracyclins. In 3 cases relapse was confined to the CNS, while diffuse relapse in 8 others included 4 cases of CNS involvement. Eight patients are now alive in CR (5 in first CR, 1 in second CR and 2 in third CR) with a median follow-up of 68.5 months (range 54-101). Chemotherapy thus emerges as the initial treatment of preference for localized testicular lymphoma. Therapy should be preceded by a thorough assessment of the stage of disease and due to the high frequency of CNS relapse, CNS prophylaxis should be considered for all patients.

Adult↗

[Salvage therapy of relapsing or refractory malignant lymphoma with non-myelotoxic combined chemotherapy. Results of combination of cisplatin, bleomycin, methyl-GAG and prednisolone (Cis-BMP)].

Fifty-one patients with primary refractory or relapsed malignant lymphoma (47 non-Hodgkin's lymphoma and four Hodgkin's disease) were treated with a new chemotherapeutic regimen (cisplatinum, methyl GAG, bleomocyin, methyl prednisolon). Among these 51 patients, 41 had measurable disease. Three of these 41 patients achieved complete remissions (7.3%) and 17 showed partial response (41.5%). The low hematological toxicity of this chemotherapeutic combination allowed us to give the full dose at the planned cycle date in 90% of the cycles. No major toxicity were observed (two minor neurological toxicities, one ototoxicity associated with oral mucositis toxicity, 6 febrile episodes) during 164 courses. With a median follow-up of 12 months, 18% of patients were alive without disease. We conclude that in this particular population of malignant lymphomas, Cis-BMP is an effective therapy with minimal toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Second primary cancers in patients continuously disease-free from Hodgkin's disease: a protective role for the spleen?

Second primary cancers are a serious late occurrence for patients surviving Hodgkin's disease (HD). In addition to previously described risk factors such as age, gender, clinical stage, and treatment modalities, splenectomy was found to correlate with an increase in risk for secondary acute leukemia. We assumed that splenic irradiation inducing functional hyposplenia and splenectomy could have similar consequences on second cancer risk. We studied a series of 892 continuously disease-free HD adult patients treated at a single institution between 1960 and 1984. The risk of second cancer was analyzed (1) relative to the general population and (2) between risk subgroups using the Cox proportional hazards model. Fifty-six patients developed a second cancer (8 acute leukemias, 3 myelodysplastic syndromes, 8 non-Hodgkin's lymphomas, and 37 solid tumors; basal cell and in situ cervix carcinomas were excluded). The 15-year cumulative incidence rate (with 95% confidence limits) was 13.2% (9.3% to 17.2%). Relative to the general population incidence data, the risk of second cancer was multiplied by 4.68 (3.51 to 6.12; P < .001); it was multiplied by 2.80 (1.63 to 4.48; P < .001) in patients whose spleen was not treated and multiplied by 6.87 (4.81 to 9.51; P < .001) in splenectomized patients or patients whose spleen was irradiated. Multivariate regression analysis that controlled for confounding variables (age, gender, clinical stage, extent of radiation therapy, and chemotherapy regimen) showed that, in addition to age above 40 years (relative risk [RR] = 3.72; P < .001), combination of MOPP chemotherapy and regional irradiation (RR = 4.99; P = .015) and combination of MOPP chemotherapy and extended irradiation (RR = 10.86; P < .001), splenic irradiation (RR = 3.67; P = .003), and splenectomy (RR = 2.54; P = .018) also significantly correlated with an increased risk. The results of this hospital-based registry study strongly suggest that splenic irradiation and splenectomy might increase the risk for treatment-related second cancer. These findings, if confirmed, have to be considered in future HD treatment policies.

Adolescent↗

Prevention of oral mucositis in patients treated with high-dose chemotherapy and bone marrow transplantation: a randomised controlled trial comparing two protocols of dental care.

Between February 1986 and November 1989, 166 patients who were candidates for a bone marrow transplantation entered a randomised controlled clinical trial to compare limited oral hygiene care (LIM) and intensive oral hygiene care (INT) in the prevention of mucositis. Randomisation was stratified on the initial oral status (good vs. bad IOS). Intensive oral hygiene care included an initial treatment of dental lesions and tooth and gum brushing during aplasia. Limited oral hygiene care excluded preventive dental treatment and gingival and tooth brushing. Mucositis was classified as absent, mild, moderate or severe, according to the clinical aspects of the different sites in the mouth and to two scales of pain evaluation. Of the 150 evaluable patients (75 in each group), 134 developed moderate/severe mucositis (64 in the INT group and 70 in the LIM group) (log-rank test P < 0.02). The superiority of intensive oral care was observed both in patients with and without total body irradiation (TBI) and in patients with a good or bad IOS; the observed risk of mucositis was reduced by 70% in each of these four subgroups. Duration of moderate/severe mucositis was, although not significantly, lower in the INT group (17 days, S.D. = 12) than in the LIM group (19 days, S.D. = 13). The median time of mucositis occurrence was 11 days in the INT group and 9 days in the LIM group. Contrary to a widespread belief, the percentage of documented septicaemia was not higher in patients who underwent intensive oral care. We conclude that, although statistically significant, the superiority of intensive oral hygiene care is not clinically impressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Radiotherapy after ovarian transposition: ovarian function and fertility preservation.

The outcome of ovarian function preservation and fertility after ovarian transposition was examined in women treated for cancer. Of 134 patients, 126 were treated with radiotherapy and 72 with chemotherapy. In a multivariate analysis, three factors appeared to be prognostic of ovarian castration: the age over 25, MOPP chemotherapy and a total dose to the ovaries higher than 5 Gy. The incidence of birth was lower in the general population but no abnormality was observed.

Adolescent↗