Successful treatment of a patient with two hematologic tumors: double-hit lymphoma and acute myelomonoblastic leukemia

Abstract

Double-hit (DH) lymphoma, an extremely aggressive variant of B-cell lymphoma, is accompanied by chromosomal abnormalities leading to the activation of a few oncogenes, one of which is the c-MYC gene in conjunction with BCL2 or BCL6 gene rearrangements. There are most common cases of MYC/8q24 and BCL2/18q21 gene rearrangements (MYC/BCL-2 DH lymphoma). The tumor is characterized by an aggressive clinical course and a poor response to chemotherapy (CT). The median survival in patients with DH lymphomas varies from 4.5 to 18 months. Such patients are generally resistant to CHOP-21 and R-CHOP-21 therapy regimens. For the treatment of patients with DH lymphoma, the Hematology Research Center, Ministry of Health of the Russian Federation, chose an original BL-M-04 polychemotherapy (PCT) protocol in combination with rituximab, followed by autologous stem cell transplantation (allo-SCT). The paper describes the experience in successfully treating a patient with two hematologic tumors: 1) MYC/BCL-2 DH lymphoma with high-dose PCT cycles, followed by allo-SCT, and 2) a metachronously developed second tumor (acute myelomonoblastic leukemia (AMML)) with CT cycles, followed by auto-SCT. The incidence of tumors induced by the previous high-dose CT for aggressive lymphomas for 10 years is 0.7 to 10%. As a rule, the development of secondary AMML is preceded by a history of myelodysplastic syndrome (MDS); characteristic chromosomal abnormalities (deletions of the long arm of chromosomes 5 and 7) are detectable. In this case, the follow-up was 3 months before the development of AMML, during this period the patient was not found to have laboratory signs of MDS (anemia, thrombocytopenia) or chromosomal abnormalities associated with secondary MDS/AML. The presence of a leukemic stem cell is associated with the occurrence and development of hemoblastosis; that of the similar cell populations that may cause B-cell lymphomas remains uncertain. The described case may have defect in a hematopoietic stem cell that gives rise to both germs of hematopoiesis, as well as complete donor chimerism of bone marrow hematopoiesis, which gives hope to long-term remission in both DH lymphoma and AMML.

Full Text

Успешное лечение больного с двумя гематологическими опухолями: "double-hit"-лимфомой и острым миеломонобластным лейкозом. - Аннотация "Double-hit" (DH)-лимфома - чрезвычайно агрессивный вариант В-клеточной лимфомы, сопровождается хромосомными нарушениями, приводящими к активации нескольких онкогенов, один из которых ген с-MYC в сочетании с перестройкой генов BCL2 или BCL6. Наиболее часто встречаются случаи с реаранжировкой генов MYC/8q24 и BCL2/18q21 (MYC/BCL2 DH-лимфома). Опухоль характеризуется агрессивным клиническим течением и плохим ответом на химиотерапию (ХТ). Медиана продолжительности жизни больных DH-лимфомами варьирует от 4,5 до 18 мес. Как правило, такие пациенты резистентны к применению режимов терапии по схемам CHOP-21, R-CHOP-21. В Гематологическом научном центре МЗ РФ для лечения больных DH-лимфомой выбран оригинальный протокол полихимиотерапии (ПХТ) ЛБ-М-04 в комбинации с ритуксимабом с последующим выполнением трансплантации аутологичных стволовых клеток крови (ауто-ТСКК). В статье представлен опыт успешного лечения пациента с двумя гематологическими опухолями: MYC/BCL2 DH-лимфомы - высокодозными курсами ПХТ с последующей ауто-ТСКК и метахронно-развившейся второй опухоли (острого миеломонобластного лейкоза - ОММЛ) - курсами ХТ с последующей ауто-ТСКК. Частота возникновения опухолей, индуцированных предшествующей высокодозной ХТ агрессивных лимфом в течение 10 лет, составляет от 0,7 до 10%. Как правило, развитию вторичного ОММЛ предшествует анамнез миелодиспластического синдрома (МДС), выявляются характерные хромосомные нарушения (делеции длинного плеча 5-й и 7-й хромосом). В данном случае период наблюдения за пациентом составил 3 мес до развития ОММЛ, в который у больного не отмечено лабораторных признаков МДС (анемии, тромбоцитопении), не обнаруживались хромосомные нарушения, ассоциированные с вторичным МДС/ОММЛ. Существование стволовой лейкемической клетки ассоциировано с началом и развитием гемобластоза; существование похожих клеточных популяций, которые могут приводить к развитию В-клеточных лимфом, остается неопределенным. Возможно, в представленном случае имелся дефект стволовой гемопоэтической клетки, давшей начало обоим росткам гемопоэза, полный донорский химеризм костномозгового кроветворения, что дает надежду на длительную ремиссию как DH-лимфомы, так и ОММЛ.
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