We report the data of 340 children with poor-prognosis solid tumors who had 592 PBSC harvests on cell separators after mobilization mainly by different treatment protocol chemotherapy regimens followed by G- or GM-CSF (94% of patients) or by G-/GM-CSF alone (6%). Timing of procedure was predicted by studying the blood count. When the WBC and platelet reached a median of 17,5 (0,9–109) and 182 (11–782) ×10 9 /L, respectively, the median number of 3,8 (0,1–22,7) ×10 6 CD34 + /kg with 1,6 (0,006–18,9) ×10 6 CD34 + /kg for 1 blood volume processed was obtained per procedure. In the group of 128 patients with low body weight [median 14,2 (8–20) kg] 176 LP were successfully performed. The extracorporal line was primed with donor RBC in the patients with the weight below 12 kg. We observed no difference in CD34 + content in harvests whether CSF was begun on d+1 or on d+3 after chemotherapy or in later in the phase of hematopoiesis recovery.

Высокодозная химиотерапия с трансплантацией аутологичных клеток-предшественников гемопоэза является стандартным методом лечения больных с чувствительными рецидивами неходжскинских лимфом (НХЛ) высокой и промежуточной степени злокачественности. До 40-60% больных сохраняют резистентность к стандартным дозам цитостатиков, и результаты лечения этой группы пациентов даже с применением высокодозной химиотерапии остаются неудовлетворительными. Использование моноклональных антител к CD20-антигену (мабтера) на разных этапах высокодозного лечения (индукция ремиссии со стандартными дозами цитостатиков, сбор стволовых клеток, высокодозная химиотерапия совместно с высокими дозами цитостатиков и после трансплантации) позволяет рассчитывать на улучшение результатов терапии больных с В-клеточными лимфомами за счет увеличения противоопухолевого действия цитостатиков (синергизм) и контроля минимальной остаточной болезни (резидуальная опухоль, клетки лимфомы, реинфузированные вместе с аутологичным трансплантатом). Анализировали результаты лечения всех больных с НХЛ, получавших высокодозную химиотерапию с трансплантацией аутологичных клеток-предшественников гемопоэза в РОНЦ им. Н.Н. Блохина РАМН с января 1989 г. по март 2005 г. За этот период высокодозное лечение получили 50 больных (20 женщин, 30 мужчин). Мабтера на разных этапах терапии была использована у 22 пациентов. На момент проведения высокодозной химиотерапии (ВХТ) средний возраст больных составил 32 года (16-58 лет). Для унификации данных и дальнейшей оценки результатов были сформированы группы больных в зависимости от агрессивности опухоли. Был проведен анализ факторов, влияющих на общую и безрецидивную выживаемость больных с агрессивными и крайне агрессивными лимфомами. Использование мабтеры на различных этапах лечения больных с В-клеточными лимфомами привело к статистически значимому улучшению общей выживаемости (р=0,037).

Aim. To study efficacy of htuximab in patients with resistant B-cell lymphoma on high-dose chemotherapy. Material and methods. From September 2000 to April 2002 we studied efficacy and tolerance of rituximab at different stages of high-dose chemotherapy. The treatment was given to 10 patients with histologically verified CD20+ non-Hodgkln's lymphoma: diffuse large-cell (n = 4), Berkitfs (n = 2), follicular (n - 3), mantle-cell (n = 1). Five patients with diffuse large-cell lymphoma and Berkitt's lymphoma had a primary resistant course of the disease, one patient with diffuse large-cell lymphoma had a refractory recurrence. Follicular and mantle-cell lymphomas were characterized by a resistant course and large tumar masses. The patients received 1-2 courses of induction chemotherapy with dexa-BEAM with collection of peripheral stem cells followed by high-dose chemotherapy (BEAM-9, CBV+mitoxantron-1) with transplantation of autologous stem blood cells. Rituximab infusion (375 mg/m2) was conducted before the collection of the stem cells, prior to high-dose chemotherapy and in posttransplantation period after recovery of hemopoiesis. Results. 4 patients achieved complete remission, 3 - partial remission, 2 had progression and 1 - stabilization. In mean follow-up 11 (2-20) months 7 of 10 patients were alive, overall survival being 15 + 2.4 months (95% confidence interval 10-19.7), median was not reached. 5patients are in complete remission: 2 of them without further treatment, 3 - after progression and repeat therapy including rituximab and interferon-a or rotuximab and CHOP chemotherapy. Conclusion. The addition of rituximab can improve the results of high-dose chemotherapy of patients with non-Hodgkin's lymphoma resistant to standard doses of cytostatics. Repeat use of this drug can be effective in some patients with progression after high-dose chemotherapy with rituximab.

AIM:To study efficacy of rituximab in patients with resistant B-cell lymphoma on high-dose chemotherapy.MATERIAL AND METHODS:From September 2000 to April 2002 we studied efficacy and tolerance of rituximab at different stages of high-dose chemotherapy. The treatment was given to 10 patients with histologically verified CD20+ non-Hodgkin's lymphoma: diffuse large-cell (n = 4), Berkitt's (n = 2), follicular (n = 3), mantle-cell (n = 1). Five patients with diffuse large-cell lymphoma and Berkitt's lymphoma had a primary resistant course of the disease, one patient with diffuse large-cell lymphoma had a refractory recurrence. Follicular and mantle-cell lymphomas were characterized by a resistant course and large tumor masses. The patients received 1-2 courses of induction chemotherapy with dexa-BEAM with collection of peripheral stem cells followed by high-dose chemotherapy (BEAM-9, CBV + mitoxantron-1) with transplantation of autologous stem blood cells. Rituximab infusion (375 mg/m2) was conducted before the collection of the stem cells, prior to high-dose chemotherapy and in posttransplantation period after recovery of hemopoiesis.RESULTS:4 patients achieved complete remission, 3-partial remission, 2 had progression and 1-stabilization. In mean follow-up 11 (2-20) months 7 of 10 patients were alive, overall survival being 15 +/- 2.4 months (95% confidence interval 10-19.7), median was not reached. 5 patients are in complete remission: 2 of them without further treatment, 3-after progression and repeat therapy including rituximab and interferon-alpha or rotuximab and CHOP chemotherapy.CONCLUSION:The addition of rituximab can improve the results of high-dose chemotherapy of patients with non-Hodgkin's lymphoma resistant to standard doses of cytostatics. Repeat use of this drug can be effective in some patients with progression after high-dose chemotherapy with rituximab.

The authors examined 8 patients with pretreated relapsing or resistant solid tumors (Wilms'--4, rhabdomyosarcoma--3, synovial sarcoma--1) who received 16 courses of chemotherapy: iphosphamide, 1800 mg/m2/day (days 1-5), vepeside, 100 mg/m2/day (days 1-5), and carboplatin 500 mg/m2/day (day 1) (IVC) and 18 courses of therapy wherein iphosphamide was replaced by cyclophosphanum, 400 mg/m2/day (days 1-5) (CVC). The patients received 2-4 induction courses (n = 18) and 1-5 consolidation courses (n = 16) with reinfusion of peripheral stem cells (PSC). All PSC separations were performed after the first or second courses of IVC/CVE. There were no significant increases in the duration of leukopenia and thrombocytopenia, in the incidence of infection with a higher ordinal of a course performed by PSC maintenance. The findings suggest that the small doses of PSC stimulated by colony-stimulating factor can maintain hemopoiesis and decrease the rate of the estimated bone marrow depletion long after repeated courses of chemotherapy in patients with prognostically poor solid tumors.

High-dose chemotherapy using transplantation of hemopoietic precursor cells offers much advantage for treatment of prognostically unfavorable cancers of the breast. Both experimental and clinical evidence points to a potential of raising antitumor effect by increased dosage of chemical drugs. Clinical studies using high-dose chemotherapy for treating patients with stage II-III tumors or with greater than or equal to 10 positive axillary lymph nodes, and locally-advanced and disseminated tumor established a relative rise in overall and recurrence-free survival, as compared with standard treatment. Hazardous cytopenia and related complications can be significantly reduced when hemopoietic precursor cells are transplanted from peripheral blood.

Transfusion of allogenic bone marrow to prevent metastasizing of osteogenic sarcoma was studied as an alternative to aggressive chemotherapy in cases when it is impossible to preserve the limb. The study was carried out on 62 dogs with spontaneous osteogenic sarcoma. A single preoperative transfusion of allogenic bone marrow was carried out in 42 dogs one day before the limb amputation and 20 animals were treated by surgery alone (amputation or exarticulation). All the animals were observed for the rest of their lives. In comparison with the control, in the group treated by bone marrow transfusion the median of metastases-free period was notably longer: 20 dogs survived for a long time, some of them died from natural causes in old age. Relative indications for bone marrow transfusion in osteogenic sarcoma are defined with consideration for age and tumor volume.

Eighteen patients with relapsed or refractory Hodgkin's disease (HD) have been treated with high-dose chemotherapy (BEAM regimen) followed by autologous peripheral stem cells and/or bone marrow rescue. There were no treatment-related deaths. Overall response rate was 82%. With a median follow-up of 10 months (3-24 months) overall survival and freedom from progression were 100 and 94% (95% confidence interval 58-97%), respectively. The use of peripheral stem cells in addition to bone marrow resulted in a significant shortening of the time to engraftment (p < 0.01). The BEAM regimen is an effective conditioning schedule which is well tolerated.

Eighteen patients with relapsed or refractory Hodgkin's disease (HD) have been treated with high-dose chemotherapy (BEAM regimen) followed by autologous peripheral stem cells and/or bone marrow rescue. There were no treatment-related deaths. Overall response rate was 82%. With a median follow-up of 10 months (3-24 months) overall survival and freedom from progression were 100 and 94% (95% confidence interval 58-97%), respectively. The use of peripheral stem cells in addition to bone marrow resulted in a significant shortening of the time to engraftment (p < 0.01). The BEAM regimen is an effective conditioning schedule which is well tolerated.

Peripheral mononuclears under normal hemopoiesis and after chemotherapy or/and cytokin were isolated on blood cell separator and cryopreserved. The cells from 22 patients with different hematological and solid malignancies were examined. Mononuclears with high content of hemopoiesis precursors may be collected rapidly after stimulation. Fast and persistent recovery of hemopoiesis in transplantation of this material after superhigh-dose chemotherapy of prognostically unfavourable patients is demonstrated. Cytokin (granulocytic and granulocytic-macrophagal growth factors) promoted fast and reliable production of sufficient quantities of peripheral blood hemopoiesis cells precursors.

Peripheral mononuclears under normal hemopoiesis and after chemotherapy or/and cytokins were isolated on blood cell separator and cryopreserved. The cells from 22 patients with differrent hematological and solid malignancies were examined. Mononuclears with high content of hemopoiesis precursors may be collected rapidly after stimulation. Fast and persistent recovery of hemopoiesis in transplantation of this material after superhigh-dose chemotherapy of prognostically unfavourable patients is demonstrated. Cytokins (granulocytic and granulocytic-macrophagal growth factors) promoted fast and reliable production of sufficient quantities of peripheral blood hemopoiesis cells precursors.