[Primary mediastinal large B-cell lymphoma in pregnant women].

AIM: To elaborate a management tactic for pregnant women with primary mediastinal large B-cell lymphoma (PMLBL) and to assess the toxicity of its treatment to the mother and fetus. SUBJECTS AND METHODS: In 2004 to 2014, the Hematology Research Center, Ministry of Health of Russia, treated 94 patients with mediastinal large B-cell lymphoma, 7 (7.4%) of them developed the disease during pregnancy. Induction therapy was performed according to the VACOP-B or R-EPOCH program. For consolidation, polychemotherapy (PCT) was made after 3-4 weeks postpartum in accordance with the R+Dexa-BEAM program, followed by radiotherapy (RT) applied to a residual mediastinal mass in a total focal dose of 36 Gy. To assess the nature of the residual mass, positron emission tomography was carried out 1 month following the induction and consolidation cycles of PCT. RESULTS: PCT was performed in 5 and 2 of the 7 patients diagnosed with PMLBCL in the second and third trimesters according to the VACOP-B and R-EPOCH programs, respectively; for consolidation, PCT was done using the R+Dexa-BEAM regimen in 7 patients: 10 men and 29 women whose ages were 18 to 60 years (median age 30 years); in 5 of the 7 patients, RT was applied to the residual mediastinal region in a total focal dose of 36 Gy. After induction treatment, 4 of 5 the patients in the VACOP-B group achieved partial remission; one of the 5 patients was stated to have disease progression. In the R-EPOCH group, 2 of the 2 patients achieved partial remission. After performing the treatment protocol, an early recurrence was recorded in 1 of the 5 cases in the VACOP-B/Dexa-BEAM/RT group. Effective autologous stem cell transplantation was carried out in patients with disease progression and early recurrence. Seven children (3 boys and 4 girls) were born. Their median body weight was 2182 g (1700 to 3600 g); the median height was 47 cm (40 to 53 cm). Two neonatal infants born to women who had received CT using the R-EPOCH regimen were diagnosed as having intrauterine pneumonia resulting from respiratory distress syndrome, which might be associated with fetal prematurity and the use of rituximab. One baby born to a patient who had been included in the VACOP-B treatment protocol was stated to have superior vena cava at birth. The median follow-up of the patients and born infants was 35 months (15 to 64 months). CONCLUSION: Due to the elaborated algorithm for the treatment and management of pregnant women, all the patients are alive without tumor signs and their babies are healthy without signs of development defects and retardation.

[Experience with high-dose chemotherapy in patients with testicular diffuse large B-cell lymphoma].

AIM: To evaluate the efficiency of high-dose therapy according to the DLBL-CNS-2007 protocol in patients with testicular diffuse large B-cell lymphoma (DLBL). SUBJECTS AND METHODS: Out of 408 male patients with non-Hodgkin lymphoma, 8 patients aged 50 to 69 years (median age 55.5 years) with primary testicular (n=3) or with generalized-stage testicular DLBL (n=5) were included in the study. These patients were followed up at the Hematology Research Center, Ministry of Health of the Russian Federation, in 2007 to 2013. Systemic chemotherapy was performed in accordance with the DLBL-CNS-2007 protocol. RESULTS: The DLBL-CNS-2007 protocol was implemented in first-line therapy in 7 patients. At the first diagnostic stage, one patient was found to have anaplastic seminoma; in this connection right orchifuniculectomy was carried out, followed by radiotherapy applied to the scrotal region in a total focal dose of 34 Gy. This patient with disease recurrence was included in the DLBL-CNS-2007 treatment protocol. The number of polychemotherapy (PCT) cycles (n=4 or 6) was determined by the time to achieve complete remission. After completion of DLBL-CNS-2007 PCT, 6 patients achieved complete remission; the primary resistant disease was noted in 2 cases. At this moment 6 patients are alive in first complete remission during the median follow-up of 50 months (10-54 months). CONCLUSION: The findings suggest that high-dose therapy according to the DLBL-CNS-2007 protocol in patients with testicular DLBL can achieve complete remission and increase overall and event-free survival rates. This fact should be borne out by a large number of observations.

[Eight-year experience in treating aggressive mediastinal large B-cell lymphomas].

AIM: To make a differential diagnosis of diffuse large B-cell lymphoma (DLBCL) with primary involvement of the mediastinal lymph nodes (LN) and primary mediastinal large B-cell lymphoma (PMLBCL); to evaluate the efficiency of a modified NHL-BFM-90 (M-NHL-BFM-90) program in the treatment of the above nosological entities. SUBJECTS AND METHODS: The investigation enrolled 60 patients with large B-cell lymphoma (LBCL) with primary involvement of mediastinal LN who had been treated at the Hematology Research Center, Ministry of Health of Russia, in 2004 to 2012. The diagnosis of PMLBCL and DLBCL with primary involvement of mediastinal LN was based on histological findings, the phenotype of tumor cells, and molecular evidence. Treatment was performed according to the M-NHL-BFM-90 program. Three pregnant women received predelivery polychemotherapy (PCT) according to the VACOP-B protocol and continued to have a DexaBEAM chemotherapy regimen 3-4 weeks postpartum. In case of a residual mass, all the patients underwent consolidation radiotherapy to the mediastinal area in a total focal dose of 36 Gy. RESULTS: The diagnosis of PMLBCL was established in 39 patients: 10 men and 29 women whose ages were 18 to 60 years (median age 30 years); DLBCL with primary involvement of mediastinal LN was verified in 21 patients: 8 men and 13 women whose age was 21 to 70 years (median age 30 years). After m-NHL-BFM-90 treatment protocol, 5-year overall survival rates in the patients with DLBCL with primary involvement of mediastinal LN and in those with PMLBCL were 95+/-5 and 86+/-6% and 5-year event-free survival rates were 95+/-5 and 78+/-7%, respectively. All the pregnant women diagnosed with PMLBCL who had received the VACOP-B --> delivery--> Dexa-BEAM PCT regimen during pregnancy achieved remission. The follow-up periods were 30, 36, and 42 weeks. CONCLUSION: The patients with new-onset LBCL and primary involvement of mediastinal LN are a heterogeneous group that includes patients having two different diagnoses: PMLBCL and DLBCL. The efficiency of high-dose PCT is different in the patients with DLBCL with primary involvement of mediastinal LN and in those with PMLBCL (in spite of their similar clinical features, similar epidemiological characteristics, and the presence of the same unfavorable prognostic factors at onset).

[Long-term results of treatment for T-cell lymphoblastic lymphomas].

AIM: To define the efficiency of the GMALL 2002 program for the treatment of patients with T-cell lymphoblastic lymphomas (T-LBL). SUBJECTS AND METHODS: Twenty-five patients with a verified diagnosis of T-LBL were examined. Male/female ratio was 19:6; median age was 33 (range 16-67) years. There was a preponderance of patients with the generalized stages of the diseases: 2, 5, and 18 with Stages II, III, and IV, respectively. Mediastinal lesion was found in 20 (80%) of the 25 patients. Their treatment was performed according to the GMALL 2002 program and similar CHOP courses. Analysis was made in 2 groups that were not different in their clinical and morphological characteristics. Group 1 consisted of 17 of the 25 patients treated according to the GMALL programs; Group 2 comprised 8 patients who had similar CHOP and other chemotherapy regimens. RESULTS: In Group 1, 15 (88%) patients achieved a complete clinical and hematological remission and 2 (12%) patients died in the first stages of the treatment. No relapses were noted. The median survival had not been achieved; 5-year overall survival was 88 +/- 8%. In Group 2, three patients were alive; 2 completed their treatment; 5 (63%) patients died from treatment failures. The median survival was 23 +/- 18%; 5-year overall survival was 45%. CONCLUSION: The findings suggest that the GMALL 2002 programs are highly effective in treating patients with T-LBL at the first stage of treatment.

[Nine-year experience in the treatment of patients with diffuse large B-cell lymphosarcoma].

AIM: To ascertain indications to standard (CHOP-21/R-CHOP-21) and intensive (mNHL-BFM-90) treatment in patients with diffuse large B-cell lymphosarcoma (DLBCL) with involvement of lymphoid organs. MATERIAL AND METHODS: The trial, performed from January 2002 to December 2010, enrolled 139 DLBCL patients with affected lymph nodes (LN), tonsils, spleen, bone marrow (BM). The diagnosis was made according to WHO criteria. The patients were examined according to the protocol of lymphoproliferative diseases. Biopsy material from all 139 patients was studied immunohistochemically on paraffin blocks (LN, tonsils, spleen, BM) using a wide panel of antibodies. The same examinations of BM were made in all 18 cases of BM involvement. Cytogenetic examination was performed in 106 patients: 48 standard cytogenetic tests, 139 - FISH for t (14;18) as well as rearrangement of locus 3q27. Patients with a poor prognosis (n = 86, 61.8%) received intensive therapy according to mNHL-BFM-90 program. The signs of a poor prognosis were the following: massive tumor (tumor size more than 7.5 cm), invasion into the adjacent organs or tissues, stage III-IV disease by Enn-Erbor, high concentration of LDG. Patients without a poor prognosis (n = 53, 38.2%) received standard treatment CHOP-21 (n = 28) or R-CHOP-21 (n = 25). RESULTS: A complete remission without recurrences was achieved in all 53 patients without signs of unfavourable prognosis (100%). Overall 5-year survival was 96%, 2 patients died in remission of other causes. Of 86 patients with a poor prognosis a complete remission was achieved in 64 (74.4%) patients. Overall and recurrence-free 5-year survival was 65 and 86%, respectively. CONCLUSION: Standard treatment provided long-term complete remission in all the patients without poor prognosis. Intensive (mNHL-BFM-90) treatment produced the best results in generalized lesion without BM involvement. Overall 5-year survival was 84% in these patients and 12% in patients with BM involvement.

[Diffuse large B-cell lymphoma with primary involvement of mediastinal lymph nodes: diagnosis and treatment].

AIM: To diagnose diffuse large B-cell lymphosarcoma (DLBCLS) with primary involvement of the mediastinal lymph nodes (LN) and to evaluate the efficiency of aggressive polychemotherapy (PCT). SUBJECTS AND METHODS: The study included 15 patients (6 men and 9 women aged 18 to 70 years; median 38 years) followed up at the Hematology Research Center, Russian Academy of Medical Sciences, in 2004 to 2009. Three and 12 patients had Stages II and IE DLBCLS, respectively. B symptoms were found in 14 (93.4%) patients. Increased lactate dehydrogenase (LDH) concentrations were detectable in 14 (93.4%) patients; tumors of 10 cm or more (bulky disease) were seen in 11 (73.3%). Enlarged cervical, supraclavicular, and axillary lymph nodes were found in 9 (60%) patients; lung involvement via extension in 9 (60%), and invasion into the pericardium in 5 (33.3%) and soft tissues of the anterior thoracic wall in (13.3%). There were no signs of involvement of extranodal organs at the moment of diagnosis. All the 15 patients received PCT according to the modified NHL-BFM-90 program: 4 to 6 courses depending on the response to the therapy; 10 (66.6%) and 5 (33.3%) patients had 4 and 6 courses, respectively; for consolidating purpose, 11 (78.5%) patients were prescribed radiotherapy applied to the mediastinum in a cumulative dose of 36 Gy due to the fact that they had a residual mass. RESULTS: Thirteen (86.6%) patients achieved a complete remission (CR). Primary PCT resistance was confirmed in one case. Another patient was stated to have near-complete remission. No recurrences were notified during the follow-up. The mean CR duration was 24.5 (range 2-49) months. CONCLUSION: DLBCLS with primary LN involvement is an individual nosological entity to be differentiated from primary mediastinal large B-cell lymphosarcoma. In most cases, DLBCLS shows signs of a poor prognosis, which makes it necessary to perform aggressive PCT.