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Haematologica 1997This study examines the occurrence of solid tumor (ST) in relation to the different types of therapy (radiotherapy, chemotherapy and radiochemotherapy; splenectomy or... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVE
This study examines the occurrence of solid tumor (ST) in relation to the different types of therapy (radiotherapy, chemotherapy and radiochemotherapy; splenectomy or splenic irradiation vs no splenectomy-no splenic irradiation) received by patients treated for Hodgkin's disease (HD).
METHODS
The study included 1,045 HD patients treated at the Department of Radiation Oncology, the Institute of Radiology and the Department of Human Biopathology, Hematology Section, University of Rome, "La Sapienza", from 1972 to 1992. For 23% of the patients the follow-up period was longer than 10 years. The average follow-up period was 72 months. For a more accurate calculation of the risk of ST occurrence, the patients were first divided into 3 subgroups according to initial treatment and then according to the total treatment they had received. Moreover, to establish a probable connection between solid tumor and splenic treatment the patients were also divided into 3 subgroups (splenectomy, splenic irradiation and no splenectomy/no splenic irradiation).
RESULTS
We recorded twenty-four cases of ST after initial treatment. Secondary solid tumor showed a cumulative risk of 0.2% and 13.4% at 5 and 20 years, respectively. After initial treatment with radiotherapy (RT) alone, the cumulative risk was 1.7% and 5.2% at 10 and 20 years, respectively; in the chemotherapy (CT) group, it was 2.4% and 18.1%; in the CT(+)RT group, it was 1.7% and 9%. No statistically significant differences were observed among the different types of treatment (splenectomy, splenic irradiation or no splenectomy/no splenic irradiation) as regards the occurrence of ST. According to multivariate analysis, the most important factor in the risk of ST was age (> 40). Relative risk was 5.2, p = 0.0001.
INTERPRETATION AND CONCLUSIONS
We conclude that an age of over 40 at diagnosis and treatment with CT alone greatly increase the risk of solid tumor occurrence.
Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Female; Follow-Up Studies; Glyoxal; Hodgkin Disease; Humans; Ifosfamide; Italy; Male; Mechlorethamine; Middle Aged; Multivariate Analysis; Neoplasms, Second Primary; Prednimustine; Prednisone; Procarbazine; Radiotherapy; Risk; Spleen; Splenectomy; Survival Analysis; Vinblastine; Vincristine
PubMed: 9107084
DOI: No ID Found -
Annals of Hematology Oct 1996Cytarabine ocfosfate (YNK01) is a novel orally applicable prodrug of cytosine arabinoside. Recent pharmacokinetic studies have revealed a prolonged release of the... (Clinical Trial)
Clinical Trial
Response to cytarabine ocfosfate (YNK01) in a patient with chronic lymphocytic leukemia refractory to treatment with chlorambucil/prednisone, fludarabine, and prednimustine/mitoxantrone.
Cytarabine ocfosfate (YNK01) is a novel orally applicable prodrug of cytosine arabinoside. Recent pharmacokinetic studies have revealed a prolonged release of the cytotoxic agent cytosine arabinoside (araC) from hepatocytes into the systemic circulation, resulting in a half-life of approximately 24 h for araC. The specific pharmacokinetic characteristics of cytarabine ocfosfate lead to a prolonged exposure of leukemic cells to this antineoplasstic agent during the 14-day cycle. the oral applicability during outpatient treatment and the sustained antineoplastic activity of araC against slowly proliferating leukemic B-cells suggest that cytarabine ocfosfate might be a useful drug in the treatment of chronic lymphocytic leukemia. Four years after diagnosis of B-CLL, a 50-year-old patient was started on cytarabine ocfosfate. Sequentially, the patient's disease had proved refractory to treatment with chlorambucil/prednisone (31 months), fludarabine (5 months), and prednimustine/mitoxantrone (3 months). These established regimens were discontinued because of increasing lymphocytosis, significant thrombocytopenia, and progressive B-symptoms. Following three cycles of cytarabine ocfosfate B-symptoms resolved, lymphadenopathy disappeared, and thrombocytopenia was significantly reduced. The patient has been free of these symptoms on a dosage of 1500 mg cytarabine ocfosfate/day (cycle of 14 days with intervals of 14-21 days) for 24 months and remains in an ongoing partial remission.
Topics: Administration, Oral; Antimetabolites, Antineoplastic; Arabinonucleotides; Cytidine Monophosphate; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Prodrugs
PubMed: 8890711
DOI: 10.1007/s002770050229 -
Cancer May 1996There is very little experience reported in the literature on the treatment of patients with relapsed or resistant human immunodeficiency virus-related non-Hodgkin's... (Clinical Trial)
Clinical Trial
Second-line chemotherapy in human immunodeficiency virus-related non-Hodgkin's lymphoma: evidence of activity of a combination of etoposide, mitoxantrone, and prednimustine in relapsed patients.
BACKGROUND
There is very little experience reported in the literature on the treatment of patients with relapsed or resistant human immunodeficiency virus-related non-Hodgkin's lymphoma (HIV-NHL). We performed a prospective study to evaluate the feasibility and activity of a second-line chemotherapy regimen consisting of etoposide, mitoxantrone, and prednimustine (VMP) in this setting.
METHODS
Twenty-one patients were consecutively treated. Thirteen patients were resistant to primary chemotherapy and 8 patients had relapsed after their first complete remission (CR). Etoposide and prednimustine were both given orally at doses of 80 mg/m2 daily for 5 days, and mitoxantrone was given intravenously at a dose of 10 mg/m2 on Day 1; the cycles were repeated every 3 weeks.
RESULTS
Nineteen of 21 patients were evaluable for response. The median number of cycles administered was 2 (range, 1-5). A CR occurred in 5 of 19 patients (26%; exact 95% confidence interval; 9-51%). Four of these CRs were observed in the 7 evaluable relapsed patients. Of 45 cycles evaluable for toxicity, severe neutropenia (< 500/microL) occurred in 19 (42%) cycles and severe thrombocytopenia (< 25,000/microL) in 6 (13%) cycles. One toxic death occurred due to sepsis during neutropenia. The overall median survival was 2 months (range, < 1-13 months); the median survival time for the 5 patients with CR (13 months; range, 6-13 months) was statistically significantly longer than that observed in patients without CR (2 months; range, < 1-7 months).
CONCLUSIONS
Although the overall prognosis of patients with resistant or relapsed HIV-NHL is very poor, palliative therapy with VMP can be effective and relatively safe in the latter group. Prolonged survival has been observed in some patients who had relapsed after initial chemotherapy.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; HIV Infections; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitoxantrone; Prednimustine; Prognosis; Prospective Studies; Recurrence; Survival Rate
PubMed: 8640681
DOI: 10.1002/(SICI)1097-0142(19960515)77:10<2127::AID-CNCR25>3.0.CO;2-W -
Leukemia May 1996The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. German Low-Grade Lymphoma Study Group.
The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) in patients with advanced low-grade non-Hodgkin's lymphomas in way of a prospective randomized multicenter trial. Two hundred and forty-six patients with stage III or IV centroblastic-centrocytic (CB-CC (Kiel-classification)) or follicle center lymphoma (FCL (REAL classification)) and centrocytic (CC) or mantle-cell-lymphoma (MCL) were randomized for therapy with either PmM or COP and are fully evaluable for response and toxicity. PmM consisted of prednimustine 100 mg/m2/day on days 1-5 and mitoxantrone 8 mg/m2 /day days 1 and 2, while COP comprised cyclophosphamide 400 mg/m2/day on days 1-5, vincristine 1.4 mg/m2/day on day 1 and prednisone 100 mg/m2/day on days 1-5. Both regimens were repeated for a total of six cycles followed by an additional two courses for consolidation in responding cases and a subsequent second randomization for interferon alpha maintenance vs observation only. Overall response rates were comparable with 83% complete and partial remissions after COP and 84% remissions after PmM. PmM revealed a significantly higher rate of complete remissions (36 vs 18%, P < 0.006), the majority being achieved after four courses. The more rapid and possibly also more effective reduction of the lymphoma cell mass by PmM resulted in a tendency to a longer event-free interval for patients achieving remissions after PmM as compared to COP with estimated median event-free intervals of 31 vs 14 months, respectively (P=0.04). Separate analysis of lymphoma subtypes showed a tendency to a lower rate of complete remission in CC or MCL as compared to CB-CC or FCL (16 vs 30%, P=0.12, NS) while overall response rates were in a similar range (81 vs 85%). In both subtypes, PmM induced a higher rate of complete remission while overall response rates were comparable after PmM or COP. Treatment associated side-effects comprised predominantly myelosuppression and granulocytopenia in particular which was more frequently observed after PmM than COP (43 vs 31 %, P < 0.0001). This difference was clinically irrelevant, however, since serious infectious complications were encountered in less than 3% of cycles after both regimens. COP therapy was associated with a significantly higher incidence and degree of hair loss and complete alopecia (31 vs 2%) as well as of peripheral neurotoxicity (23 vs 2%). These data show that both PmM and COP reveal a high anti-lymphoma activity in patients with advanced stage non-Hodgkin's lymphoma. PmM appears advantageous with a higher rate of complete remissions and a better tolerability with regard to secondary side-effects. A longer follow-up is needed to assess the long-term effects of initial treatment on disease-free and overall survival and the impact on additional maintenance therapy with interferon alpha.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Female; Humans; Hydrocortisone; Lymphoma, Non-Hodgkin; Male; Methotrexate; Methylprednisolone; Middle Aged; Mitoxantrone; Prednimustine; Remission Induction; Treatment Outcome; Vincristine
PubMed: 8656680
DOI: No ID Found -
European Journal of Cancer (Oxford,... Dec 1995Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of disorders which can either be classified according to their biology, represented by corresponding counterparts... (Review)
Review
Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of disorders which can either be classified according to their biology, represented by corresponding counterparts of normal lymphocyte development as in the Kiel classification, or according to their clinical course, used in the Working Formulation. The recently proposed Revised European-American Lymphoma (R.E.A.L.) classification may unify both aspects and facilitate the comparability of international studies. Besides histology, the extent of disease still comprises the major determinant of therapy. In high-grade lymphomas combination chemotherapy with cyclophosphamide, hydroxydaunorubin, vincristine and prednisone (CHOP) represents the treatment of first choice, and may be restricted to 3-4 cycles in patients with limited stages of the disease when followed by involved field radiotherapy. In more extended, bulky stage II to IV disease, treatment must be extended to six courses of CHOP and, potentially, additional irradiation. Even in advanced states of the disease, long-term remission and potential cure are achieved in 30-50% of cases. In low-grade lymphomas, most patients present with advanced stages III and IV for which chemotherapy can be applied with palliative intention only. Hence, a watch-and-wait approach still seems appropriate outside clinical investigations until the disease requires a therapeutic intervention. This consists preferentially of chemotherapy of moderate intensity such as cyclophosphamide, vincristine and prednisone (COP) or prednimustine and mitoxantrone (PmM). In responding patients, maintenance therapy with interferon-alpha is currently being explored and may result in prolongation of disease-free and, possibly also, overall survival. In both high- and low-grade lymphomas, intensification of therapy by myeloablative chemotherapy or combined chemoradiotherapy followed by autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation provides a promising and potentially curative prospective. In addition, new cytostatic agents such as the purine analogues--fludarabine, chlorodeoxyadenosine and deoxycoformycin--enlarge the therapeutic spectrum. More experimental approaches consist of the application of immunotoxins or radioisotypes, coupled to monoclonal antibodies directed against lymphoma-specific antigens. Overall, the substantial advances that have been achieved in the understanding of the biology and pathogenesis of malignant lymphomas, as well as the current achievements of therapy and the new promising perspectives, justify the hope that curative therapy can soon be offered to an increasing proportion of patients with NHL.
Topics: Humans; Lymphoma, Non-Hodgkin; Palliative Care; Risk Factors; Treatment Outcome
PubMed: 8652232
DOI: 10.1016/0959-8049(95)00367-3 -
Blood Nov 1995Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many... (Comparative Study)
Comparative Study
Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts.
Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34+ cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensitive to stem cell-toxic chemotherapy. PBPC should be harvested before repeated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blood Cells; Bone Marrow; Bone Marrow Transplantation; Carmustine; Cell Survival; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Female; Glyoxal; Graft Survival; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Multivariate Analysis; Prednimustine; Prednisolone; Prednisone; Procarbazine; Radiotherapy; Retrospective Studies; Salvage Therapy; Vinblastine; Vincristine
PubMed: 7579368
DOI: No ID Found -
Nihon Sanka Fujinka Gakkai Zasshi Mar 1995A new therapeutic strategy for advanced ovarian cancer is to administer ultra-high doses of anticancerous drugs, followed by peripheral blood stem cell transplantation...
A new therapeutic strategy for advanced ovarian cancer is to administer ultra-high doses of anticancerous drugs, followed by peripheral blood stem cell transplantation (PBSCT) to recover normal marrow functions. There are, however, no clear regimens to induce mobilization of peripheral blood stem cells (PBSCs). We therefore used three different chemotherapies and granulocyte colony-stimulating factor (G-CSF) to produce a rebound increase in PBSCs during myelosuppression by apheresis. Eleven patients with advanced ovarian cancer (FIGO Stage; IIc-1, IIIc-5, IV-4, Recurrence-1) received chemotherapy with CEP (cyclophosphamide: 500-750mg/m2, epirubicin: 50-70mg/m2, cisplatin: 70mg/m2), CEE (cyclophosphamide: 2,000mg/m2, epirubicin: 50mg/m2, etoposide: 300mg/m2, and PEC salvage (cisplatin: 75mg/m2, etoposide: 300mg/m2, cyclophosphamide: 1,000mg/m2) followed by lenograstim (G-CSF; 2 micrograms/kg subcutaneous injection daily for 14-18 days) to mobilize PBSCs. A range of 0-38.2 x 10(4) (mean +/- S.D.; 11.1 +/- 5.0 x 10(4) colony forming unit granulocyte-macrophage (CFU-GM)/kg in the CEP regimen (n = 15), 1.6-40.8 x 10(4) (mean +/- S.D.; 12.3 +/- 3.6 x 10(4) CFU-GM/kg in the CEE regimen (n = 11), and 8.6-11.4 x 10(4) (mean +/- S.D.; 10.0 +/- 2.0 x 10(4) CFU-GM/kg in the PEC salvage regimen (n = 2) were recruited by a single apheresis. Although the CEE regimen to mobilize PBSCs was much more efficient than the CEP regimen, a large number of PBSCs showing 38.2 x 10(4) CFU-GM/kg were mobilized by the CEP regimen with a dose-escalation of cyclophosphamide 750mg/m2 and epirubicin 70mg/m2. The number of CFU-GM/kg correlated well with that of CD34+ (r = 0.693).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Separation; Cisplatin; Cyclophosphamide; Epirubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Lomustine; Ovarian Neoplasms; Prednimustine
PubMed: 7535329
DOI: No ID Found -
Tumori Dec 1994Although initial treatment of Hodgkin's disease induces a complete remission in most patients, approximately 50% of patients with advanced disease will not achieve a... (Clinical Trial)
Clinical Trial
AIMS AND BACKGROUND
Although initial treatment of Hodgkin's disease induces a complete remission in most patients, approximately 50% of patients with advanced disease will not achieve a complete remission or will relapse following the first complete remission.
PATIENTS AND METHODS
Twenty-three patients with relapsed/resistant Hodgkin's disease, observed between January 1991 and October 1993, underwent CEP combination chemotherapy (CCNU, etoposide, prednimustine). All patients had previously received MOPP and ABVD regimens, in combination at diagnosis or sequentially (at diagnosis and at the first relapse).
RESULTS
Thirteen (56%) patients achieved complete responses and 4 (18%) had partial responses. Two partial responders obtained a complete remission after a successive autologous bone marrow transplantation. The complete remission was not influenced by the timing of MOPP and ABVD treatments, presence of extranodal involvement or presence of bulky disease, but was affected by the presence of a primary disease refractory to the first standard programs. All the complete responders but 2 were alive and relapse-free at a median follow-up of 15 months; no major toxic effects were recorded.
CONCLUSIONS
These data suggest, as did those of other studies, that CEP is an effective regimen in patients with Hodgkin's disease in first or second relapse, also to reduce the tumor burden and to determine chemosensitivity before contingent bone marrow or peripheral blood stem cell support.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Resistance; Etoposide; Female; Hodgkin Disease; Humans; Lomustine; Male; Middle Aged; Prednimustine; Recurrence; Survival Analysis; Treatment Outcome
PubMed: 7900233
DOI: 10.1177/030089169408000606 -
Haematologica 1994A fundamental principle in the therapeutic strategy for recurrent lymphomas is the employment of agents that are not part of the usual front line combination regimens.... (Clinical Trial)
Clinical Trial
BACKGROUND
A fundamental principle in the therapeutic strategy for recurrent lymphomas is the employment of agents that are not part of the usual front line combination regimens. Ideally, the cytotoxic agents should lack complete cross resistance with those utilized up front.
PATIENTS AND METHODS
A three-drug combination of ifosfamide, epirubicin and etoposide (IEV) was used to treat 20 patients with relapsing or refractory high-grade non-Hodgkin's lymphoma (HG-NHL) or Hodgkin's disease (HD).
RESULTS
Of 14 patients with HG-NHL, 5 (36%) achieved a complete response (CR) and 4 partial remission (PR), giving an overall response rate of 64%. To date, all the complete responders are still in CR at +5, +5, +6, +7, and +9 months, respectively. Of 6 patients with HD, 4 (66%) obtained CR and 2 PR, giving an overall response rate of 100%. The 4 CRs are still in remission after +4, +5, +9, and +13 months, respectively. Clinical and hematologic toxic effects were moderate: neutropenia was responsible for delaying treatment for a week in 6 patients.
CONCLUSIONS
These results confirm the efficacy of the IEV regimen in inducing a good remission rate with moderate side effects in relapsing/refractory HG-NHL and HD patients and they show that further investigations with this combination are warranted.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Doxorubicin; Drug Resistance; Epirubicin; Etoposide; Female; Fluorouracil; Hodgkin Disease; Humans; Ifosfamide; Leucovorin; Lomustine; Lymphoma, Non-Hodgkin; Male; Mechlorethamine; Methotrexate; Middle Aged; Prednimustine; Prednisone; Procarbazine; Remission Induction; Salvage Therapy; Treatment Outcome; Vinblastine; Vincristine
PubMed: 7534744
DOI: No ID Found -
Journal of the National Cancer Institute Oct 1994There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between...
BACKGROUND
There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described.
PURPOSE
Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL.
METHODS
Within a cohort study of 11,386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls.
RESULTS
Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose < .05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P < .05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P < .05). Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8;95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (< 20,000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy.
CONCLUSIONS
Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10,000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Female; Humans; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Logistic Models; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms, Second Primary; Radiotherapy; Registries
PubMed: 8089863
DOI: 10.1093/jnci/86.19.1450