Results of treating acute myeloblastic leukemia in patients over 60 years of age

An efficiency of the acute myeloblastic leukemia therapy has been assessed in 79 patients aged over 60 years. Twenty six patients out of this group have been treated with usual or reduced doses of doxorubicin and cytarabine (ADR-Ara-C) 35--low doses of cytarabine (LD Ara-C), 11-6-mercaptopurine (6 MP), and 7 patients died before chemotherapy. Complete remission in group treated with ADR-Ara-C was achieved in 23% of patients while partial remission in 42%. Median survival in this group was 5.8 months (range from 0.5 to 16 months). Percentage of the complete remissions in the group treated with LD-Ara-C was 6%, and partial remissions 40%. Median survival was 4.7 months (range from 0.5 to 14.2 months). Partial remission in 5 out of 11 patients treated with 6 MP (36%) and no complete remissions were noted. Median survival was 3.9 months. Therapy with ADR-Ara-C produced marked leucopenia and thrombocytopenia in the majority of treated patients. Vomiting, hemorrhagic complications, and bacterial infections have also been noted. These adverse reactions have been less frequent in patients treated with LD-Ara-C, and 6 MP. Ten patients (38%) treated with ADR-Ara-C and 7 patients treated with LD-Ara-C died during remission inducing therapy.     

Combination Chemotherapy using L-Asparaginase,Daunorubicin, and Cytosine Arabinoside in Adults with Acute Myelogenous Leukaemia

Cytosine arabinoside and daunorubicin used in an intensive intermittent regimen have been shown to be an effective combination for the induction of complete remissions in 14 out of 23 adult patients with acute myelogenous leukaemia. This gives an overall complete remission rate of 60%. A further patient had a good partial remission. The addition of L-asparaginase to the regimen has not increased the incidence of remission and there were more side effects in the L-asparaginasetreated group. Of the 10 patients treated with L-asparaginase in addition to cytosine arabinoside and daunorubicin, five achieved a complete remission. Of the 13 patients treated with cytosine arabinoside and daunorubicin without L-asparaginase, nine achieved a complete remission and one a good partial remission.     

A modified MOPP regimen in the treatment of Hodgkin's disease stage III B and IV (author's transl)

In a retrospective study 80 patients with Hodgkin's disease of stage III B (n = 32) and IV (n = 48) were investigated, who had been treated with a modified MOPP regimen. 28 patients (35%) were previously untreated. A completed remission was reached in 51 patients, a partial remission in 16, and 13 patients failed to respond. 16 patients had died in the observation period. Complete remissions were twice as frequent with 90% in stage III as compared with 45% in stage IV. The group of patients surviving 4 years was 92% in stage III and 62% in stage IV.     

Treatment of acute myeloblastic leukemia in adults: remission induction with a combination of cyclophosphamide,cytarabine and vincristine

A regimen of intravenous cyclophosphamide, cytarabine and vincristine, given over a four-day period and repeated every two to three weeks, was used to treat 33 patients with acute myeloblastic leukemia. Of the 30 evaluable patients 9/18 previously untreated patients achieved complete remission and two others marked improvement, and 4/12 previously treated patients achieved complete remission. Twelve of 16 patients under the median age of 38 responded while only 3/14 patients over this age responded. There was no difference in response between those with elevated muramidase levels and those with normal levels. Three patients developed a previously unrecognized syndorme of fever, malaise, rash and orbital suffusion. Cytarabine was probably responsible.At least four courses of treatment are required before abandoning this regimen of therapy. Patients who achieve a complete remission and live for more than 150 days spend about 25% of their total survival time from diagnosis in hospital.     

Prolonged remission maintenance in acute myeloid leukaemia.

Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.     

Clinical and cell kinetic data on the combination of cytosine arabinoside with daunorubicin, isosfamide, thioguanine, and vincristine for remission induction and maintenance in patients with acute myelocytic leukaemia (author's transl)]

31 adult patients (study A) with acute myelocytic leukaemia were treated for remission induction with cytosine arabinoside (ARA-C, 100 mg/m2/day) by a 7 (5) day continuous infusion. 3 (2) doses of daunorubicin (DNR, 45 mg/m2 i.v.) were added at daily intervals. For maintenance 5 day ARA-C was given monthly in sequential combination with DNR, thioguanine (TG), or ifosfamide (IFOS). 16 (52%) patients achieved complete remission (C.R.) after 1.8 (1-3) courses and 6.7 (3-10) weeks from treatment start. The median survival for responders and non-responders was 11.5 months, early death rate within 6 weeks was 3 (10%). Median remission duration was 13.5 months. Among 11 patients surving for 7-22 months 7 patients are in first remission for 5.5-20.5 months. DNR, IFOS and TG were given before the 3rd day of ARA-C infusion. In a previous group of 34 leukaemic patients and in 44 therapy courses DNA histograms of bone marrow cells using pulse cytophotometry showed marked accumulation in S-phase for 75% of courses. Also (G2 + M)-cells in the DNA distribution and thymidine pulse labelling indices were markedly increased in most cases, whereas thymidine uptake by scintillation counter was diminished and mitotic indices had not changed significantly. In now 15 patients (study B) the induction regimen was intensified by adding vincristine (VCR, 2 mg i.v.) and 3 doses of IFOS (600 mg/m2 i.v.). Preliminary results are 50% C.R. after 1,7 (1-2) courses and 6.8 (5-10) weeks from initiation of therapy. 2 patients died in the first 6 weeks.     

Response-oriented therapy with CHOP and VIM-Bleo in high-grade malignant non-Hodgkin's lymphomas

Twenty four patients with high grade malignant NHL (stage II 8, stage III 4, stage IV 12 patients respectively) were treated with a response-oriented regimen: Treatment was initiated according to the CHOP-protocol. Patients achieving at least a partial remission after 2 and a complete remission (CR) after 4 cycles were continued on CHOP to a total of 9 cycles. Patients not meeting these criteria were switched to a combination of Etoposide, Ifosfamide, Methotrexate, and Bleomycin (VIM-Bleo). With CHOP treatment, 16 patients (67%) achieved a CR. Of the remaining 8, 7 were treated with VIM-Bleo; 5 of these entered CR for a overall CR rate of 21/24 (88%). With a median follow up of 28 months 7 patients relapsed: 6 relapses occurred in patients with a rapid initial response and treated only with CHOP. We conclude, that there is a significant risk of relapse even in patients readily responding to CHOP and that consolidation therapy with a non cross-resistant regimen may improve results in these patients.     

PAD方案治疗75例初诊多发性骨髓瘤疗效观察

目的:PAD方案已成为目前多发性骨髓瘤(MM)治疗的一线方案,国内外就其疗效和不良反应发生均有报道,本实验旨在观察并探讨PAD方案治疗我中心初诊多发性骨髓瘤患者的疗效和不良反应,为临床工作提供参考。方法:我科75例初诊多发性骨髓瘤患者给予PAD方案4-6疗程,评估疗效及不良反应。结果:75例患者接受PAD方案化疗,四疗程后总有效率(CR+VGPR+PR)为73.3%,其中CR 5例,占6.7%,VGPR 12例,占16%,PR 38例,占50.7%;无效例数为20例,占26.7%,其中SD 17例,占22.7%,PD 3例,占4%;1年总生存率为75%,2年总生存率为62.7%。血液学不良反应有白细胞降低34例(45.3%),血小板降低10例(13.3%);非血液学不良反应有周围神经系统症状25例(33.3%),疱疹病毒感染7例(9.3%),消化系统症状15例(20%),乏力14例(18.7%),呼吸系统症状29例(38.7%),激素相关症状3例(4%)。绝大部分患者可以耐受且完成相应化疗疗程。结论:我中心PAD方案疗效令人满意,不良反应可耐受,同国内外报道的疗效反应率相近,不良反应发生率更低,是治疗多发性骨髓瘤的首选方案。     

Remission induction and remission maintenance in adult acute nonlymphocytic leukemia employing a modified cytostatic (COAP) regimen.

Thirty adult patients suffering from acute nonlymphocytic leukemia (ANLL) were treated according to a modified COAP regimen. Vincristine, cyclophosphamide, and prednisone were given by push injection, while cytosine arabinoside was infused over periods of 8 h. Nineteen patients (63%) achieved complete remission. Remission maintenance therapy consisted of 6-mercaptopurine daily and methotrexate twice weekly. Later in the study, COAP consolidation and reinduction was added, which improved the median duration of complete remission from 7 to 24 months. Comparison of the results with the literature shows that the modified COAP regimen is one of the most effective treatment schedules for adult ANLL.     

Hyper-CVAD/MA治疗复发或难治性弥漫大B 细胞淋巴瘤的临床研究

目的:探讨Hyper-CVAD/MA方案治疗复发或难治弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的疗效及安全性。方法:观察26例经系统化疗后复发或难治的DLBCL患者接受Hyper-CVAD/MA方案化疗,21-28天为1周期,连续2个周期评价疗效及安全性,分析生存情况。结果:全组26例患者中,总有效率为46.15%,其中完全缓解(complete remission,CR)3例(11.54%),部分缓解(partial remission,PR)9例(34.61%),全组患者中位生存时间为10(2-25)个月,1年和2年总生存率分别为28.57%、14.29%。不良反应主要表现为III-IV度骨髓抑制及继发的肺部感染,其他包括胃肠道反应、口腔炎、肝功能异常等。结论:Hyper-CVAD/MA治疗复发难治DLBCL有一定的疗效,且患者可耐受,可作为二线方案的一个选择。     

Evaluation of the myelogram carried out on the 6th day of remission- inducing treatment of acute nonlymphoblastic leukemia in adults as an indicator of therapeutic effectiveness

Aspiration biopsy in 31 patients with AML was performed prior to and in the 6th day of induction therapy. Studied group included 17 women and 14 men of 40 yrs mean age. Blastosis prior to and on the 6th day of the observation were compared and the index of blastosis reduction counted. Median value of blastosis reduction was 29.5%, 40% of the patients with the index below the median value showed complete remission, while the patients with the indexes above the median value obtained significantly higher number of complete remission (CR = 81%, p less than 0.05). Statistically significant reduction of leukaemic infiltration in examined myelograms was as s rule the sign of oncoming favourable therapeutic result. In cases of nonaplastic marrow with persistent blastosis (blastosis reduction 29.5%) one should consider a change of the therapeutic regimen.     

Chemotherapy in patients with progressive, undifferentiated neuroendocrine tumors: a single-center experience

Treatment of patients with undifferentiated and histologically confirmed neuroendocrine tumors (NET) usually includes chemotherapeutic intervention. This retrospective study evaluated the outcome of 2 such chemotherapies. 18 patients (11 males; age 56.2 ± 2.5) with proven progressive disease were enrolled (mean Ki-67 34 ± 5%). Patients were treated from 2005 to 2007 with regimen A (carboplatin, etoposide, paclitaxel), and from 2007 to 2009 with regimen B (cisplatin, etoposide). This change was due to low tolerability of regimen A. The standard imaging procedure was computed tomography. 8 patients underwent treatment with regimen A (mean 3.3 ± 0.7 courses). Due to severe side effects, 3 patients had their therapy prematurely discontinued. The treatment responses of 6 patients who received more than 1 course were: 0% complete response (CR), 17% partial response (PR), 50% stable disease (SD), and 33% progressive disease (PD). The median progression free survival (PFS) was 6.7 months (range 3.2-10.0). In contrast, 12 patients received regimen B (mean 3.8 ± 0.4 courses), and none of them dropped out because of side effects. The overall responses were: 0% CR, 17% PR, 42% SD, and 42% PD. The median PFS was 6.3 months (range 2.8-26.4). The response rates of both regimes were not statistically different. Patients who were treated with regimen B demonstrated comparable PFS and less severe side effects than patients who received regimen A. However, patients need to be aware of the relatively short PFS time. In order to improve therapeutic outcome of patients with progressive undifferentiated NET, new therapeutic approaches and larger multi-center studies are needed.     

Intravenous and oral demethoxydaunorubicin (NSC 256-439) in the treatment of acute leukemia and lymphoma: a pilot study

Demethoxydaunorubicin (DMDR), a new anthracycline available both for intravenous and oral administration, was given in 14 cases of leukaemia, non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) replacing either daunorubicin (DNR) or doxorubicin (DOX) in conventional chemotherapy regimes. In acute leukaemia (6 myeloblastic and 1 common lymphoblastic) there were 5 complete (CR) and 2 partial (PR) remissions; one patient, previously brought into remission with a regime including i.v. DMDR was thereafter maintained in CR with oral DMDR. Among the patients treated with the oral DMDR, 2 NHL cases were treated; 1 patient had a sustained remission of 12 months so far, with DMDR alone; another patient had a CR with a combined regime. In MM, one patient with very advanced disease treated with i.v. DMDR/CHOP did not respond, but three cases treated with oral DMDR plus other drugs showed a partial remission. Toxic effects were limited to brief episodes of nausea and vomiting in a few i.v. treated patients; a prolonged bone marrow depression was observed in one case only. No cardiotoxic effect was recorded.     

Treatment of neuroblastoma with [131I]metaiodobenzylguanidine: long-term results in 25 patients.

From 1984 to 1990 we have treated altogether 25 children with [131I]metaiodobenzylguanidine (131I-MIBG) for a refractory, relapsed or metastasized neuroblastoma. Three children had stage III and 22 children had stage IV of the disease; at diagnosis their ages were between 4 months and 10 years. Children with stage III disease had at diagnosis a median age of 3.0 years and at treatment 3.8 years. After first-line chemotherapy 2 children had achieved a complete remission (CR), while in 1 child the tumor did not respond (NR) to the initial treatment. At the time of 131I-MIBG treatment 2 children had relapsed and in the other one no further response was achievable. The children were treated by a 13.5 +/- 12.9 mCi/kg BW per course with a mean total dose of 280.7 +/- 243.9 mCi. One child achieved CR by 131I-MIBG alone, while in 2 cases no measurable success was observed. All 3 children were treated additionally by surgery, chemotherapy and bone marrow transplantation (BMT). Two children have died but one is alive and in CR. The 22 children with stage IV disease were treated in two different study groups. In group A, 14 children were studied for side-effects and response to 131I-MIBG. All children were pretreated with standard chemotherapy. Five were treated in relapse, 5 in progression and 3 at a refractory state of the disease; only 1 child was in complete remission when being treated with 131I-MIBG. Group A patients were treated with a mean of 2.4 courses, with 10.3 mCi/kg BW for each course.(ABSTRACT TRUNCATED AT 250 WORDS)     

Duration of second remission of Hodgkin's disease in children. Results of treatment achieved by the Polish Leukemia and Malignant Lymphoma Therapy in Children Group]

Recurrence was noted in 18.5% of 194 children, in which chemotherapy with MVPP regimen produced complete I remission. In 6 out of 36 children with recurrent disease MVPP regimen was repeated, while the remaining children were treated with B-DOPA alone or combined with MOPP regimen. Local radiotherapy was used in 17 children. The second complete remission was achieved in 30 (83.7%) children. Thirteen out of 36 patients died because of the progress of the disease (11 children), and for complications (2 children). Percentage of persisting 5- and 10-year II remissions are 58.2% and 54.6%, respectively. A 5- and 10-year survival rates in children with recurrent disease are 80.5% and 60.5%, respectively. Our relatively favourable results we associate--first of all--with the chemotherapy intensity.     

The so-called partial synchronization in the treatment of malignant lymphomas. A clinical study

In a randomized study the effectiveness of a modified MOPP scheme (CVPP scheme) and a so-called partial synchronisation treatment (vincristine or vinblastine respectively and cyclophosphamide) was compared in 72 patients predominantly pretreated with Hodgkin lymphomas and non-Hodgkin lymphomas. From 49 patients affected with lymphogranulomatosis of stage IIIB and IV, 24 were treated according to CVPP scheme; in 10 of them a complete remission was achieved and in 4 of them a partial remission. 25 patients were treated in the control group with synchronization therapy. In 13 of them a complete remission and in 12 of them a partial remission was achieved. With CVPP therapy the mean remission time amounted to 14.4 months and with synchronization therapy 9.2 months. There was no significant statistical difference. From 23 patients with advanced non-Hodgkin lymphomas of a high malignancy 11 received a therapy with CVPP scheme; 2 of them came into a complete remission and 3 of them into a partial one. 12 patients received a synchronization therapy; 7 of them came into a partial remission. With CVPP therapy the mean remission time amounted to 14.4 months, with partial synchronization therapy--10.8 months. Even in non-Hodgkin lymphomas there was no significant difference between the forms of therapy used. Even a comparison of the two survival times of both forms of treatment does not reveal any significance. Thus, both procedures of treatment seem to be comparable in their therapeutic efficaciousness, even if the number of complete remissions during the treatment with CVPP scheme was greater in our investigations. The assumed lower toxicity of synchronization therapy could not be confirmed by our study. In addition to the controversial synchronization effect, the good efficaciousness of treatment according to the so-called synchronization therapy may be due to sensibilizing phenomena and recruitment phenomena.     

131I]metaiodobenzylguanidine therapy in advanced neuroblastoma.

Forty-two children with advanced neuroblastoma who either failed with first-line therapy or relapsed after achieving a complete remission, were considered for treatment with [131I]metaiodobenzylguanidine (131I-MIBG). We subdivided 42 cases into 5 groups, in accordance with the stage of disease at diagnosis, response to first-line therapy and relapse. A total of 99 courses of 131I-MIBG were administered with doses ranging from 2.8 to 6.0 GBq. One child received six courses, 3 four courses, 18 three courses, 6 two courses and 15 one course of 131I-MIBG. The total delivered dose in single measurable lesions ranged from 286 to 1691 cGy with an uptake factor ranging from 3% to 10%. We obtained a major response in primary tumors, and a long-term response was observed in 5 cases, lasting more than 2 years without further chemotherapy.     

Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK-432 in combination with radiotherapy: Association of the therapeutic effect with differentiation and apoptosis in the cancer cells

Twenty patients with oral squamous cell carcinoma having mainly stage II or III lesions without distant metastasis, were treated with tegafur and streptococcal agent, OK-432, in combination with radiotherapy. As a consequence, 16 cases among the treated 20 cases showed complete remission by this therapy alone. Especially, we have found that the squamous cell carcinoma arising in non-keratinizing oral epithelium rather than in keratinizing oral epithelium has better response to this therapy. Among the 16 cases with complete remission (CR) by the current therapy, 10 cases were histopathologically diagnosed as well-differentiated squamous cell carcinoma and six cases as moderately differentiated squamous cell carcinoma. When we examined immunohistochemically the expres-sion of various antigens such as proliferating cell nuclear antigen (PCNA), p53 and LeY or the presence of DNA fragmentation by nick-end labelling in the biopsy materials taken at the first visit to our clinic from 20 patients treated with the current therapy, the CR group showed a significantly increased LeY expres-sion level ( p< 0.05) and DNA fragmentation rate ( p< 0.05) as compared with the partial response (PR, n= 3) + no change (NC, n= 1) group. On the other hand, the CR group with respect to PCNA expression level was significantly decreased as compared with the PR + NC group ( p< 0.05). From these findings, it can be considered that the therapy for oral squamous cell carcinoma by UFT and OK-432 in combination with radiotherapy is very effective, which may be associated with differentiation or apoptosis in oral squamous carcinoma cells. In addition, we present the clinical findings and results of immunohistochemical staining for the biopsy materials obtained from four CR cases treated with the current therapeutic method.     

5-FLUOROURACIL IN METASTATIC MAMMARY CANCER

Thirty patients with advanced metastatic breast cancer were treated with 5-fluorouracil. There were two deaths attributable to drug toxicity. Ten additional patients died of advancing disease, and of this group only two showed significant remissions as a result of drug therapy. Of the 18 patients surviving, 17 obtained objective and subjective remission from their disease and 12 were in complete remission from four to fourteen months from institution of therapy. In four of these cases, radiation therapy was combined with chemotherapy.     

Treatment results of nine patients with Burkitt's lymphoma

From 6/79 until 2/86, 9 patients (median age 39) with Burkitt's lymphoma were treated. Stage D disease was seen in 7 cases, stage C in two and stage A in one. The main symptom was abdominal pain or a rapidly progressing abdominal tumor. Three patients had bone marrow involvement and two had a Burkitt's leukemia. Three had typical chromosomal aberrations. Therapy consisted of a variety of chemotherapy regimens plus additional radiotherapy and/or bulk surgery. Two patients achieved complete remissions (of 6 and 20+ months duration), and 4 partial remissions were obtained. The remaining patients had either progressive, drug resistant disease or died early. One patient is currently alive and in complete remission at 20+ months. A second patient is alive at 20+ months in partial remission with traces of IgM-paraprotein still detectable. The main causes of death were tumor-lysis syndrome (4 patients) and therapy related sepsis with progressive tumor (3 patients). This poor outcome is probably due to a high proportion of high-risk patients and suboptimal therapy for this rapidly proliferating tumor.