Biomedical subjects

N Niitsu

Publications and source records attributed to N Niitsu.

At least 37 records · Page 2Linked to original sources

PubMed2000

Myeloid and monocytoid leukemia cells have different sensitivity to differentiation-inducing activity of deoxyadenosine analogs.

The differentiation-inducing effect of clinically applicable analogs of deoxyadenosine on myelomonocytic leukemia cells was examined. Monocytoid leukemia cells were more sensitive to the analogs than were erythroid or myeloid leukemia cells based on the inhibition of cell growth and induction of cell differentiation. Monocytoid leukemia cells were highly sensitive to combined treatment with 2'-deoxycoformycin (dCF) and 9-beta-D-arabinofuranosyladenine (Ara A) for inducing cell differentiation. Ara A induced the differentiation of monocytoid leukemia U937 and THP-1 cells at concentrations which were 1/1000-10000 of that at which it induced the differentiation of other cell lines in the presence of dCF. In combination with a low concentration of 1alpha,25-dihydroxyvitamin D3 (VD3), the induction of the monocytic differentiation was greater in monoblastic U937 cells. Adenosine deaminase-resistant analogs such as fludarabine (FLU) and cladribine (CdA) also induced the differentiation of human myelomonocytic leukemia cells, and these analogs synergistically enhanced the differentiation induced by all-trans retinoic acid (ATRA) or VD3. CdA was the most potent analog for inducing the differentiation of myeloid leukemia NB4 and HL-60 cells in the presence or absence of ATRA. These findings indicate that dCF + Ara A and CdA may be effective for the therapy of acute monocytoid and myeloid leukemia, respectively.

Acute Disease↗

PubMed2000

CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) regimen with granulocyte colony-stimulating factor (G-CSF) for patients with aggressive non-Hodgkin's lymphoma: a pilot study. The Adult Lymphoma Treatment Study Group (ALTSG).

We conducted a multi-institutional collaborative study to examine the usefulness and safety of third-generation chemotherapy CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) combined with granulocyte colony-stimulating factor (G-CSF) in the treatment of aggressive non-Hodgkin's lymphoma (NHL). Subjects included patients with aggressive NHL who were 60 yr of age or younger and had been diagnosed as having a low-intermediate, high-intermediate, or high risk using the International Prognostic Index (IPI). A total of 24 patients were enrolled in the study between May 1997 and March 1998, including 9 low-intermediate-risk cases, 13 high-intermediate-risk cases and 2 high-risk cases. Although all 24 patients were originally enrolled in the study, one adult T-cell leukemia/lymphoma case was subsequently excluded. Thus, in the end, 23 cases were evaluated. Evaluation of the efficacy of therapy revealed complete remission in 20 patients (87%). Of these 20 patients, 8 were low-intermediate-risk cases (89%) and 12 were either high-intermediate- or high-risk cases (86%). Partial remission was achieved in 2 patients (8.7%). The 2-yr survival rate was 91.3%, and the 2-yr disease-free survival rate was 81.8%. Grade 3 or higher adverse reactions were granulocytopenia (87%), thrombocytopenia (17.4%) and liver dysfunction (4.3%). CyclOBEAP therapy has been associated with a high remission rate for aggressive NHL. When combined with G-CSF, a high relative dose intensity was maintained for each drug administered (0.94-0.97). Furthermore, although the observation period was short, both the survival rate and disease-free survival rate were good. Hence, we concluded that there were no problems associated with the procedure in terms of safety.

Adolescent↗

PubMed2000

Elevated serum levels of soluble CD44 variant 6 are correlated with shorter survival in aggressive non-Hodgkin's lymphoma.

A variant form of CD44 that has additional amino acids in the common protein backbone (CD44-v6) seems to play a role in the metastasis of malignancies. We measured soluble CD44-v6 (sCD44-v6) by ELISA in 201 patients with malignant lymphoma. The sCD44-v6 level was significantly elevated in patients with non-Hodgkin's lymphoma (NHL) (n = 184). The sCD44-v6 level was correlated significantly with the standard sCD44 and soluble interleukin-2 receptor levels, but only weakly with serum lactate dehydrogenase (LDH). In 149 patients with aggressive NHL, the sCD44-v6 level was elevated in the subgroups with a high LDH level, stage III/IV disease, T-cell lymphoma, and high-intermediate or high risk group as identified by the International Prognostic Index (IPI). When the sCD44-v6 level was > or = 800 ng/ml the overall survival rate was significantly decreased (p = 0.0001). In the low + low-intermediate risk group (IPI) both overall survival rates (log-rank p = 0.0005, Wilcoxon p =0.002) were significantly decreased when the sCD44-v6 level was > or = 800 ng/ml. In multivariate analysis, sCD44-v6 was shown to be independent of the five prognostic factors in the IPI (age, performance status, number of extranodal sites, Ann Arbor stage and LDH level), so it may be useful for predicting the outcome of aggressive NHL.

Female↗

PubMed2000

Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity.

Pivalyloxymethyl butyrate (AN9) is an anticancer derivative of butyric acid. In this study, doxorubicin (DXR) and AN9 synergistically inhibited the growth of lymphoma and lung carcinoma cells, whereas there was no synergy between AN9 and antimetabolites. AN9 did not affect the intracellular uptake of DXR. Among anthracyclines and their derivatives, the synergistic effect was prominent in compounds with a daunosamine moiety, suggesting that AN9 may affect the catabolism of these compounds. The degradation of DXR in the extract from AN9-treated cells was much less than that in extract from untreated cells. AN9 did not directly inhibit the enzyme activity but rather suppressed expression of the enzyme. With respect to the expression of drug resistance-related genes, there was no significant difference between untreated and AN9-treated cells. However, AN9 significantly down-regulated the levels NADPH-cytochrome P450 reductase and DT-diaphorase mRNA in the presence of DXR but not the level of xanthine oxidase mRNA. The enhancement of the sensitivity to anthracyclines was closely associated with the suppression of the mRNA expression.

Antibiotics, Antineoplastic↗

PubMed2000

Vidarabine and 2-deoxycoformycin as antileukemic agents against monocytic leukemia.

Although 2'-deoxycoformycin (dCF) has been reported in clinical trials to be less effective against myeloid than lymphoid malignancies, it may be useful for treating monocytic leukemia with the aid of 2'-deoxyadenosine (dAd) analogs. In the presence of 10 microM dAd, the concentration of dCF required to inhibit the viability of monocytoid leukemia cells was much lower than that required on normal or non-monocytoid malignant cells in primary culture. Among the dAd analogs, 9-beta-D-arabinofuranosyladenine (AraA) was also effective in combination with dCF. Although dCF alone slightly but significantly prolonged the survival of mice inoculated with U937 monocytic leukemia cells, combined treatment with dCF and AraA markedly prolonged the survival. These results suggest that the combination of dCF and AraA may be useful for the clinical treatment of acute monocytic leukemia.

Animals↗

PubMed1999

Prognostic implications of the differentiation inhibitory factor nm23-H1 protein in the plasma of aggressive non-Hodgkin's lymphoma.

The outcome of patients with non-Hodgkin's lymphoma has been improved by current approaches to treatment. Nevertheless, many patients either do not have a complete remission or ultimately relapse. To identify such patients, it is important to be able to predict the outcome. We previously found that the differentiation inhibitory factor/nm23 was correlated with the prognosis of acute myeloid leukemia. To examine the prognostic effect of nm23 on non-Hodgkin's lymphoma, we established an enzyme-linked immunosorbent assay procedure to determine nm23-H1 protein levels in plasma and assessed the association of this protein level with the response to chemotherapy, overall survival, and progression-free survival in patients with aggressive non-Hodgkin's lymphoma. The plasma concentration of nm23-H1 was significantly higher in patients with malignant lymphoma than in normal controls, especially in aggressive non-Hodgkin's lymphoma. The complete remission rate in patients with higher nm23-H1 levels was significantly worse than that in patients with lower nm23-H1 levels. Overall survival and progression-free survival were also lower in patients with higher nm23-H1 levels than in those with lower levels. The 3-year survival rates in patients with low and high nm23-H1 levels were 79.5% and 6. 7% (P =.0001). A multivariate analysis of prognostic factors showed that the plasma nm23-H1 level was independently associated with the survival and progression-free survival. An elevated plasma nm23-H1 concentration predicts a poor outcome of advanced non-Hodgkin's lymphoma. Therefore, nm23-H1 in plasma may be useful for identifying a distinct group of patients at very high risk.

Adult↗

PubMed1999

A high serum soluble Fas/APO-1 level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma.

Soluble Fas (sFas) in the serum is believed to be able to inhibit apoptosis of lymphocytes. It has been reported that the serum sFas level is increased in various diseases, including malignant lymphoma and systemic lupus erythematosus. We studied the association between sFas and the prognosis of patients with aggressive non-Hodgkin's lymphoma (NHL). Compared with normal controls, the serum sFas level was increased significantly in patients with aggressive NHL and adult T cell leukemia/lymphoma. Among patients with aggressive NHL, the complete remission rate was significantly decreased in the subgroup having high serum sFas levels. Both the overall survival rate and the disease-free survival (DFS) rate were significantly lower for this subgroup than for patients with low serum sFas levels. The 5-year survival rates estimated by the Kaplan-Meier method for patients with high and low serum sFas levels were 27.6% and 68.3%, respectively (P = 0.0001). The 5-year DFS rates estimated for patients with high and low serum sFas levels were 44.7% and 71.9%, respectively (log-rank test: P = 0.0023, and generalized Wilcoxon test: P = 0.0014). Among patients with a low and low-intermediate risk group according to the International Prognostic Index (IPI), the 5-year survival rates for low and high serum sFas subgroups were 72.8% and 42.0%, respectively, showing a significant difference (Wilcoxon test: P = 0.0163, log-rank test: P = 0.0115). Among patients with a high-intermediate and high risk group, the 5-year survival rates for low and high serum sFas subgroups were 51.6% and 17.4%, respectively, again showing a significant difference (Wilcoxon test: P = 0.0001, log-rank test: P = 0.0002). Multivariate analysis of a series of prognostic factors, including the five used to calculate the IPI, showed that the serum sFas level was an independent prognostic factor for the overall survival. Based on these results, a serum sFas level of 10 ng/ml or more can be considered to indicate a poor prognosis in patients with advanced NHL, and this finding may be useful for developing strategies for further treatment.

Adolescent↗

PubMed1999

Response and adverse drug reactions to combination chemotherapy in elderly patients with aggressive non-Hodgkin's lymphoma: comparison of CHOP, COP-BLAM, COP-BLAM III, and THP-COPBLM.

We retrospectively compared therapeutic results and adverse events in 198 elderly patients (> or = 70 yr old) with aggressive non-Hodgkin's lymphoma diagnosed between 1981 and 1995 who underwent CHOP, COP-BLAM, COP-BLAM III, or THP-COPBLM chemotherapy. Complete remission (CR) was achieved in 138 patients (69.7%). The CR rate was 47.0% for CHOP, 76.3% for COP-BLAM, 67.9% for COP-BLAM III, and 74.4% for THP-COPBLM therapy (p = 0.013). The 5-yr survival rate was 37.0% for CHOP, 49.0% for COP-BLAM, and 53.5% for COP-BLAM III. The event-free survival rate showed no significant differences between the four treatments. Adverse events of Grade 3 or worse were commonly anemia or granulocytopenia in patients receiving THP-COPBLM therapy. Cardiac sympathetic dysfunction and cardiac mitochondrial damage were less common with pirarubicin than with doxorubicin. For elderly patients, it is better to select therapy with as few adverse events as possible based on the complications and medical history of the individual patients.

Aged↗

PubMed1999

Non-Hodgkin's lymphoma in the elderly: a guide to drug treatment.

Adverse events are common in the elderly when they undergo potent chemotherapy and the reasons for this are various. Therefore, chemotherapy for elderly patients with non-Hodgkin's lymphoma (NHL) must differ from that for non-elderly patients. Age is one of the poor prognostic factors for NHL and the main reason for this is reduced antitumour effect due to decreased dose and increased adverse effects. However, many of these elderly patients also die from causes other than lymphoma. The usual approach to the treatment of indolent NHL is to use drugs with few adverse effects such as nucleoside analogs. Multidrug therapy is used for intermediate grade NHL and the most commonly used regimen is CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). In recent years, many clinical trials have been performed in elderly patients with NHL. The results of these trials indicate that a significantly better prognosis is achieved with anthracycline (cytostatic antibiotics) containing regimens. The elderly population will continue to grow and so it is necessary to establish more effective treatment options for NHL in the elderly.

Age Factors↗

PubMed1999

Adenosine analogs as possible differentiation-inducing agents against acute myeloid leukemia.

Several adenosine analogs induce the functional and morphological differentiation of myelomonocytic leukemia cells. They can be classified into two types; i.e., those that do/do not require phosphorylation to induce the differentiation of leukemia cells. Neplanocin A, a potent S-adenosylhomocysteine hydrolase inhibitor, induces the differentiation of some leukemia cells without phosphorylation. On the other hand, deoxycoformycin (dCF), a potent adenosine deaminase inhibitor, also induces the myelomonocytic differentiation of leukemia cells when it is treated with deoxyadenosine (dAdo). This differentiation is inhibited by 5'-amino-deoxyadenosine, an inhibitor of (deoxy)adenosine kinase, suggesting that kinase-dependent phosphorylation is involved in the differentiation-inducing effect of dCF plus dAdo. Retinoids induce the differentiation of NB4 cells, a cell line derived from human promyelocytic leukemia. When used in combination with all-trans retinoic acid (ATRA), both NPA and dCF plus dAdo greatly enhance the granulocytic differentiation of NB4 cells. This enhancing effect is greatest when the cells are pretreated with NPA and then with ATRA. On the other hand, pre-exposure of NB4 cells to ATRA greatly potentiates the differentiation induced by dCF plus dAdo, while pretreatment with dCF plus dAdo before exposure to ATRA is less effective. The ATRA-induced differentiation of NB4 cells is effectively augmented by clinically applicable concentrations of these analogs. A clinical strategy that combines intermittent treatment with these analogs and a low dose of ATRA may increase the clinical response and decrease the adverse effects of ATRA.

Adenosine↗

PubMed1999

[COP-BLAM therapy for a Hodgkin's disease in the elderly].

Hodgkin's disease (HD) is a disorder with a better prognosis than non-Hodgkin's lymphoma and it predominantly affects young persons. In association with the aging of the population, however, HD has been increasing among persons aged 65 years and over in recent years. We used the COP-BLAM regimen to treat elderly patients with HD, and responses and adverse reactions were investigated. A total of 14 patients with HD treated at our department between April 1987 and December 1997 were included in this study. The patients were 8 men and 6 women aged 65 years or older, with a median age of 68 years. Five patients with clinical stage I or II disease, who had factors indicating a poor prognosis, received 3 courses of the COP-BLAM regimen with additional regional therapy of the involved field (IF). Six courses of COP-BLAM were administered to 9 patients with stage III or IV disease. The treatment was evaluable in all patients. Treatment achieved a complete remission (CR) in 12 (85.7%) of the 14 patients and a partial remission in 2 (14.3%). The CR rate was 100% for stage I or II and 77.8% for stage III or IV. The overall 5-year survival rate was 76.2% and overall disease-free 5-year survival rate was 75.7%. Adverse reactions included grade 3 or higher leukopenia in 35.7% and grade 3 or higher thrombocytopenia in 7.1%. Grade 3 or higher non-hematological toxicity included stomatitis and peripheral neuropathy in one patient each. From these results, we concluded that the COP-BLAM regimen was safe for elderly patients with HD and could achieve prolongation of survival.

Aged↗

PubMed1998

Human monocytoid leukemia cells are highly sensitive to apoptosis induced by 2'-deoxycoformycin and 2'-deoxyadenosine: association with dATP-dependent activation of caspase-3.

The adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) significantly inhibits the proliferation of leukemia and lymphoma cell lines. When cells were incubated in the presence of both dCF and 2'-deoxyadenosine (dAd), the concentration of dCF required to induce apoptosis of monocytoid leukemia cells was much lower than that required for myeloid, erythroid, or lymphoma cell lines. Among the cell lines tested, U937 cells were the most sensitive to this treatment. The concentration of dCF that effectively inhibited the proliferation of U937 cells was 1/1,000 of that required for lymphoma cell lines, on a molar basis. However, the uptake of dCF or dAd in U937 cells was comparable with that in other leukemia and lymphoma cell lines. The intracellular accumulation of dATP in U937 cells was only slightly higher than that in other leukemia cells in dCF-treated culture. Treatment with dCF plus dAd induced apoptosis in U937 cells at low concentrations, and this apoptosis was reduced by treatment with caspase inhibitors. Induction of caspase-3 (CPP32) activity accompanied the apoptosis induced by dCF plus dAd. No activation of CPP32 was observed in cytosol prepared from exponentially growing leukemia and lymphoma cells. However, dATP effectively induced CPP32 activation in cytosol from monocytoid cells, but not in that from nonmonocytoid cells, suggesting that dATP-dependent CPP32 activation is at least partly involved in the preferential induction of apoptosis in monocytoid leukemia cells. The combination of dCF and dAd may be useful for the clinical treatment of acute monocytic leukemia.

Apoptosis↗

PubMed1998

Biweekly THP-COPBLM (pirarubicin, cyclophosphamide, vincristine, prednisone, bleomycin and procarbazine) regimen combined with granulocyte colony-stimulating factor (G-CSF) for intermediate- and high-grade non-Hodgkins's lymphoma.

Biweekly THP-COPBLM including pirarubicin (THP), which is thought to be less toxic than doxorubicin, was used to treat non-Hodgkin's lymphoma (NHL) and the remission rate and adverse events were studied in 42 patients younger than 69 years. Complete remission (CR) was achieved in 37 patients (88.1%) and partial remission in five (11.9%). Classified by international prognostic index, CR was achieved in 16 out of 17 low-intermediate-risk patients, 14 out of 16 high-intermediate-risk patients and seven out of nine high-risk patients. The 3-year survival rate was 72.1% and the 3-year event-free survival rate was 58%. Grade 3 or higher adverse events included granulocytopenia in 39 patients (92.9%) and thrombocytopenia in seven (16.7%). The biweekly THP-COPBLM regimen appears useful for the treatment of aggressive intermediate- and high-grade NHL, and G-CSF made it possible to shorten the interval between courses of chemotherapy. Further studies regarding adverse events on organs, other than on bone marrow are required to improve the long-term results of combination therapy on NHL.

Adult↗

PubMed1998

Clinical features of testicular non-Hodgkin's lymphoma--focus on treatment strategy.

Testicular primary non-Hodgkin's lymphoma (NHL) is said to account for about 5% of all testicular tumors and about 2% of extranodular lymphoma. From a clinical standpoint, we reviewed testicular NHL of stage IE treated at our department over the past 18 years. Among the 865 cases of NHL, 19 (2.2%) were primary testicular NHL, stage IE. The 19 patients had a median age of 62 years (range 48-77 years), all had diffuse B-cell lymphoma. Of the 19 patients, 8 were treated with radiotherapy after high inguinal orchiectomy (Group I), 4 received both postoperative radiotherapy and chemotherapy (Group II), and 7 received additional prophylactic intrathecal chemotherapy (Group III). The 5-year survival rates for Groups I, II and III were 37.5%, 50%, and 100%, respectively. None of the patients receiving prophylactic intrathecal chemotherapy had relapse in the central nervous system and all of them are alive and disease-free. Primary testicular NHL is relatively common among elderly persons, and many patients die as a result of central nervous system recurrence. These results suggest that preventive measures for central nervous system recurrence such as intrathecal injection of anticancer agents should be taken into consideration as early as at the induction of remission.

Aged↗

PubMed1998

Pirarubicin-induced myocardial damage in elderly patients with non-Hodgkin's lymphoma.

123I-metaiodobenzylguanidine (MIBG) myocardial single photon emission computed tomography (SPECT), 123I-beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECT, and holter ECG recording were performed in patients with non-Hodgkin's lymphoma who underwent chemotherapy including pirarubicin (THP), in an attempt at early detection of cardiac toxicity from THP. Twenty-six patients with untreated non-Hodgkin's lymphoma who received THP-COPBLM therapy were studied. For THP-COPBLM therapy. THP was administered at a dose of 40 mg/m2 every 21 days and the total dose was 250 mg/m2 on average (40 approximately 400 mg/m2). 1) The washout rate (WR) correlated with the total THP dose, and was considered to be a useful index of cardiac sympathetic nervous dysfunction. 2) The left ventricular ejection fraction (LVEF) correlated negatively with the total dose of THP. 3) The total dose of THP showed a correlated positively with the extent score and severity score determined by BMIPP. 4) The WR correlated with the frequency of premature ventricular contraction. Animal studies have indicated that THP has less cardiac toxicity than doxorubicin, but the present study showed that cardiac toxicity occurred at a total THP dose of about 360 mg/m2 in elderly patients. Accordingly, when THP is used to treat elderly patients, multimodal evaluation of cardiac is necessary to detect cardiotoxicity and to determine the optimal dosage.

3-Iodobenzylguanidine↗

PubMed1998

[Clinical study of elderly patients with non-Hodgkin's lymphoma arising in the thyroid].

The study group comprised 10 patients who were referred between 1992 and 1996 with non-Hodgkin's lymphoma arising in the thyroid gland. There were three men and seven women, with a median age of 75 years, and seven of the group had a history of Hashimoto's disease. All 10 patients had hypothyroidism; anti-microsomal antibody was positive in six. The lymphoma was of the diffuse type in all patients (B cell, 9; T cell, 1). Five patients had stage I and five had stage II. Generally, four courses of COP-BLAM therapy were given, followed by radiotherapy (30 Gy). Complete remission was achieved in all patients, and they remained alive and disease-free for a median period of 40 months. Ultrasonography revealed diffuse, an-or hypoechoic confluent nodules, and there was intensification of the posterior acoustic enhancement in most patients. With early diagnosis non-Hodgkin's lymphoma arising in the thyroid of elderly patients, mainly women, can be cured with chemotherapy and radiotherapy.

Aged↗

PubMed1998

[High-dose biweekly CHOP chemotherapy with granulocyte colony-stimulating factor support for patients with aggressive non-Hodgkin lymphoma].

A pilot study of high-dose biweekly cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy with granulocyte colony-stimulating factor support was carried out at 11 centers. Twenty-five patients with aggressive non-Hodgkin lymphoma under the age of 65 years old were registered. Lowest values of leukocytes and neutrophils scored grade 3 and 4 levels of Eastern Co-operative Oncology Group Toxicity Criteria in over 50% of the courses. Very rapid recovery of leukocytes and neutrophils was observed, and the duration of leukocytes under 1,000/microliter was less than 3 days in 72.2% of the courses. Leukocyte counts exceeded 2,000/microliter within 3 days in 69.1% of the courses. In most patients the hemoglobin and platelet count remained at grade 1 or 2 levels. Fever was seen in 15 out of 110 courses. In two-thirds of the 15 courses, fever disappeared within 3 days. Thus, administration of the CHOP protocol at biweekly intervals was feasible in 76.5% of the courses. Of 22 evaluable patients, there were 11 complete (CR) and 9 partial (PR) responses with an overall response rate of 90.9%. Among 13 high risk patients excluding 9 low and low-intermediate groups by International Prognostic Index, 7 CRs (53.8%) and 5 PRs (38.5%) were observed. This protocol is promising for aggressive chemotherapy of non-Hodgkin lymphoma.

Adult↗

PubMed1998

[A clinical study of primary lymphoma of bone].

Primary non-Hodgkin's lymphoma (NHL) of bone is a rare disease, accounting for less than 1% of all NHL cases and 3-5% of all extranodal lymphoma cases. Of 512 NHL patients treated at our department, 9 patients (1.8%, median age of 54 years) had primary NHL of bone. The disease was histologically of the diffuse type in all a patient, and of the large cell type in 6. The disease was at stage 1 in 8 patients and stage II in 1. The patients all received radiotherapy of 30-40 Gy following either the CHOP or COP-BLAM chemotherapy regimens. Treatment achieved complete remission in 8 patients. Six patients still alive (median follow-up: 63 months). It has been reported that survival is longer for patients treated with a combination of chemotherapy and radiotherapy than those, treated with radiotherapy alone. Consequently, we conclude that the standard treatment course for primary NHL of bone should be chemotherapy followed by radiotherapy.

Adult↗