AIM:To compare efficacy and toxicity of conservative therapy (different programs of polychemotherapy) of gastric lymphosarcoma conducted for the last 10 years in Hematological Research Center of the Russian Academy of Medical Sciences.MATERIAL AND METHODS:The study included 63 patients (40 females and 23 males aged 14 to 78 years, mean age 49 years) with primary diagnosis of gastric lymphosarcoma (GL). Of them, 56 (89%) patients had diffuse large B-cell lymphosarcoma (DLBCL) and 7 (11%) had gastric Berkitt's lymphoma (BL). Only detection of t(8;14) with rearrangement of c-myc gene provided accurate diagnosis of gastric BL. By the treatment DLBCL patients were divided into two groups: 44 patients of group 1 received polychemotherapy (PCT) according to CHOP scheme or in combination with radiotherapy and surgical treatment; 12 patients of group 2 were treated according to modified program mNHL-BFM-90, without surgical or radiation treatment. Of 7 patients with gastric BL 5 patients received treatment according to a modified program mNHL-BFM-90 and 2 patients were given CHOP because of DLBCL misdiagnosis without cytogenetic detection of t(8;14).RESULTS:Overall survival in group 1 was 73% in mean follow-up 61 months. The survival depended only on initial factors of poor prognosis (PPF): tumor size over 10 cm, Ann-Arbor stage higher than IE, B-symptoms, elevated level of LDH. Overall survival of 18 gastric DLBCL patients without PPF reached 94%, of 26 patients with PPF - 60%. Lethality due to side effects was 4% (2 patients), primary resistance was 14% (6 patients), recurrence arose in 9% (4 patients). Overall survival in group 2 was 100% in mean remission duration 18 months, was unrelated to PPF (10 of 12 patients) but correlated with high toxicity. 5 BL patients treated with a modified mNHL-BFM-90 program achieved remission (a mean follow-up at present is 1 to 50 months, mean 24 months). 2 BL patients treated with CHOP died for a year.CONCLUSION:Gastric lymphosarcomas are sensitive to chemotherapy, thereby PCT only is effective in most patients. PPF in gastric DLBCL were responsible for poor outcome in 40% patients in CHOP treatment. The modified program mNHL-BFM-90 can produce up to 100% complete long-term remissions in therapy of gastric lymphosarcoma in adults both in BL and DLBCL patients. A cytogenetic examination of c-myc gene rearrangement is obligatory before initiation of PCT of gastric lymphosarcoma.

Aim. To compare efficacy of NHL-BFM-90 and CHOP-like courses in the treatment of anaplastic large cell lymphoma (ALCL). Material and methods. Twenty-two patients with ALCL participated in the study. The diagnosis was made basing on the findings of clinical, device, morphological, immunohistochemical and molecular-genetic examinations with application of a panel of monoclonal antibodies to CD30, ALK, CD3, CD4, CD8, CD7, CD34, CD15, CD68, CD20, CD45RO, CD45RA, Ki-67. 14 cases of 22 were negative by kinase of anaplastic lymphocytes (ALK-) and 8 were positive (ALK+). Mean age of ALK-ALCL patients was 39.6 + 4.1 years, of ALK+ALCL patients - 23.4 + 2.6 years. 14 patients were treated by the protocol NHL-BFM-90, 8 were initially treated with other schemes (CHOP, MACOP-В, BEACOPP and others). All 14 patients treated according to NHL-BFM-90 had ALCL stages III-IV with B-symptoms. 12 patients who completed treatment by the above protocol achieved complete remission after the forth course, 2 patients failed the treatment. Of 8 ALCL patients treated initially according to other schemes, a complete remission was achieved in 4 patients (2 had stage II). One of 4 patients with remission had recurrence. Four patients who had failed to achieve complete remission died of the disease progression. Conclusion. ALCL occurs more frequently in young and middle-aged patients. The disease has an aggressive course with rapid generalization. For such processes it is more preferable to use a modified protocol NHL-BFM-90.

AIM:To analyse efficacy and tolerance of high-dose polychemotherapy (PCT) of Berkitt's lymphoma (BL) in patients aged over 40 years.MATERIAL AND METHODS:High-dose PCT was given to 6 BL patients aged 41-56 years (median 48.1 years).RESULTS:Complete clinicohematological remissions were achieved in 4 patients. In two of them the treatment was discontinued after three blocks of PCT because of severe infectious complications. According to 4-12 month follow-up, remission continues. Remission was not achieved in two patients: one patient had primary resistance, the other died of sepsis after the second PCT course before remission. The time to remission did not correlate with age. Duration of myelotoxic agranulocytosis varied from 2 to 24 days. Duration of agranulocytosis did not correlate with age. Infections complicated 19 of 20 PCT blocks. Severity of complications caused withdrawal of three patients.CONCLUSION:BL is biologically heterogenous as it demonstrates different responses to BL-M-04 program. Causes of slow regression of tumor mass in some patients need further investigations. In spite of a great number of infectious complications high-dose therapy has no alternative.

The efficiency and toxicity of FNC and FNCR chemotherapy protocols in the treatment of primary orbital lymphocytoma were evaluated. The study was carried out in 10 patients. As the first-line therapy 7 patients received FNC and 3 patients received FNCR. Remission was attained in all cases. Complete responses were attained after 2 to 6 courses. The mean period of observation was 13 (3-26) months. Hematological toxicity was no higher than second degree, being observed mainly in patients of the eldest group. No adjuvant radiotherapy was carried out. Hence, FNC and FNCR protocols were effective and little toxic in patients with primary orbital lymphocytoma, no additional radiotherapy was needed.

The main aim of the new protocol was to improve the treatment efficiency for patients with Burkitt lymphoma (BL) by intensifying the therapy and contracting the duration of treatment. The study was carried out in 17 patients with the diagnosis of BL (12 men and 5 women aged 5-46 years; mean age 25 years), treated at Hematology Research Center in 2003-2005. Two patients presented with stage I (after S. B. Murphy), one with stage II, six with stage III, and eight with stage IV. Bone marrow involvement was detected in 5, neuroleukemia in 5 patients. The new protocol is based on modified pediatric protocol NHL-BFM-90 with methotrexate dose of 1.5 g/m(2). BL completely regressed in chemosensitive patients after 1-2 blocks irrespective of the initial size of the tumor, and therefore 4 blocks were planned (2 induction and 2 consolidating). The data on the highest sensitivity of the tumor to high-dose methotrexate and cytosar prompted the use of these drugs for the induction phase in order to attain the maximum cytoreducing effect. In order to attain remission, blocks A and C were used. Doxorubicin was added to block A and methotrexate to block C for intensification of therapy. Consolidating courses were similar to the induction ones. The interval between the courses was the same as previously (21 days). Seventeen patients received complete treatment according to BL-M-04 protocol. Remission has been attained in 94% patients; 88% patients are alive during the 1st complete remission (the median of observation 16.5 (5-27) months). Two patients died from chemotherapy complications: 1 from traumatic subdural hematoma in the presence of thrombocytopenia (40 x 10(9)/L) during remission of the underlying disease, the other died from fulminant candidal (Candida krusei) sepsis during remission induction. Total duration of treatment was 3-3.5 months. Unfavorable prognostic factors significantly increasing the number of complications were disease stage IV, ARF by the beginning of therapy, previous treatment, and a history of extensive (mutilating) interventions. We consider that this protocol leads to rapid regression of the tumor and accelerates the treatment due to intensification of chemotherapy with tolerable toxicity.

Aim To assess efficacy of a modified program NHL-BFM-90 in adult patients with primary diffuse large B-cell gastric lymphosarcoms (PDLBGL) with unfavourable prognosis. Material and methods Modified courses of NHL-BFM-90 were conducted in 5 patients aged 27-67 years from January 2004 to September 2005. Four patients received chemotherapy of the first line, in one patient block therapy followed monotherapy with chlorambucil and a CHOEP course. All the patients were in a severe clinical condition and had several initial factors of unfavourable prognosis: size of the tumor more than 10 cm; stage IE and more advanced; B-symptoms; proliferative activity above 70%. The program NHL-BFM-90 was modified because of the patients' age. Chemotherapy was conducted according to the middle arm of the original program NHL-BFM-90, but methotrexate was introduced in a dose 1 g/m2 for 12 hours, while leukovorin was given 18 hours after the start of methotrexate injection. In two cases the blocks were enhanced with rituximab, 2 patients had doxorubicin in block A, in one case block C was enhanced with methotrexate. A total of 23 modified blocks NHL-BFM-90 were performed: one patient was given 6 blocks, two patients--5, one patient--4 blocks and one patient--3 blocks. Results Four patients after block 2 and one patient after block 3 of polychemotherapy NHL-BFM-90 achieved remission of the disease of 6 to 22 months duration which still continues. Infectious complications related to hematological toxicity arose more frequently at the latest courses of chemotherapy. Conclusion Treatment according to the modified program NHL-BFM-90 in adult patients with PDLBGL and unfavourable prognosis is highly effective. For a mean follow-up of 10.2 months no recurrences occurred. The number of courses can be reduced to decrease accumulated hematological toxicity and in case of rapid achievement of remission.

AIM:To compare programs of chemotherapy used in adult Berkitt-like lymphoma (ABLL); to assess efficacy and toxicity of the protocol AblL-M-04.MATERIAL AND METHODS:31 ABLL patients (23 males, 8 females, mean age 27 years) participated in the study performed in Hematological Research Center in 1995-2004. ABLL stage I, II, III and IV was diagnosed in 3, 5, 8 and 15 patients, respectively. 10 patients had diffuse large B-cell lymphoma. 9 patients received 2 to 6 courses of CHOP, 1 patient--6 courses of Pro-Mace-Cytabom, 11 patients with newly diagnosed ABLL and 5 pretreated with CHOP--NHL-BFM-90. The modified protocol ABLL-M-04 of intensive short-term therapy included 10 patients, 2 of them pretreated.RESULTS:Of 10 patients given CHOP or CHOP-like courses 9 were resistant to therapy, 2 died of rapid progression, 7 were converted to the program therapy. 5 patients on the protocol NHL-BFM-90 died after short-term improvement. None of them achieved remission. Of 10 patients with newly diagnosed ABLL treated according to NHL-BFM-90 protocol, remission was achieved in 4 patients, follow-up median--34 months (2-56). Six patients died: 4 of progression, 2 of chemotherapy complications. BLL-M-04 therapy was made in 9 patients: 7 patients persisted on the first remission, 2 patients died of chemotherapy complications. Overall duration of the treatment was 3-3.5 months.CONCLUSION:The protocol ABLL-M-04 seems to be more effective than a classic NHL-BFM-90, but this must be supported by more cases. CHOP therapy cannot be recommended for patients with ABLL because of poor efficacy (all the CHOP patients died).