非霍奇金淋巴瘤治療后繼發急性髓細胞白血病M6型一例_《華西醫學》

作者：

張艷玲 ¹ , 何森 ² , 牟一 ³ , 楊洋 ⁴ , 班承哲 ⁵ ,  吳俁 ¹

四川大學（成都，610041）1 華西醫院血液科，2 華西醫院心臟內科，3 華西醫院消化內科，4 臨床醫學院，5 口腔醫學院;

關鍵詞：

治療相關性白血病非霍奇金淋巴瘤急性髓細胞白血病M6型

DOI：

CNKI: 51-1356/R.20120115.1541.003

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目的　增加對治療相關性繼發白血病的認識。方法　報道非霍奇金淋巴瘤治療后2年繼發急性髓細胞白血病M6型1例，結合文獻討論治療相關性白血病的發病機制、治療、預后。結果　1例73歲非霍奇金淋巴瘤患者接受R（Rituxmab，利妥昔單抗）－CHOP環磷酰胺+多柔比星+長春新堿+潑尼松方案規律化學治療。治療結束24+個月后，經骨髓涂片及細胞免疫分型診斷為急性髓細胞白血病M6型，染色體檢查為：44～48，XY，del（5）（q12q33），-8，-10，der（12）t（4；12）（q11-q12；p13），其一般情況急劇惡化并死亡。結論　治療相關性白血病的發生可能與烷化劑等化療藥物使用和免疫受損等有關，利妥昔單抗導致第二腫瘤的發生暫時不能除外。治療相關性白血病常伴有復雜染色體核型，其病情發展迅速，治療效果差，生存期明顯縮短。
Objective 　To improve the understanding of secondary therapy-related leukemia. Methods 　The clinical data of one patient with non-Hodgkin lymphoma which transformed into acute myeloid leukemia M6 2 years after chemotherapy were studied. We discussed the pathogenesis, treatment and prognosis of therapy-related leukemia with literature review. Results 　A 73-year-old patient diagnosed to have non-Hodgkin’s lymphoma accepted R-CHOP chemotherapy.Two years after the treatment, the disease finally developed into acute myeloid leukemia M6 confirmed by cytogenetics, bone marrow morphology and flowcytometry analysis. The chromosome analysis demonstrated complex karyotypes as 44-48, XY, del (5) (q12q33), -8, -10, der (12) t (4; 12) (q11-q12; p13). His general status deteriorated rapidly and soon after the patient died. Conclusions 　Occurrence of therapy-related leukemia may be due to the administration of alkylating agents, topoisomerase inhibitors and damage of immune function. Therapy-related leukemia often occurs with complex karyotypes and progresses rapidly with poor treatment response.

引用本文： 張艷玲,何森,牟一,楊洋,班承哲,吳俁. 非霍奇金淋巴瘤治療后繼發急性髓細胞白血病M6型一例. 華西醫學, 2012, 27(1): 14-17. doi: CNKI: 51-1356/R.20120115.1541.003 復制

1.	Armitage JO, Carbone PP, Connors JM, et al. Treatment-related myelodysplasia and acute leukemia in non-Hodgkin’s lymphoma patients[J]. J Clin Oncol, 2003, 21(5): 897-906.
2.	Sacchi S, Marcheselli L, Bari A, et al, Secondary malignancies after treatment for indolent non-Hodgkin’s lymphoma, a 16-year follow-up study[J]. Hematologica, 2008, 93(3): 398-404.
3.	Gomez GA, Friedman M, Reese P. Occurrence of acute nonlymphocytic leukemia in a prospective randomized study of treatment for Hodgkin’s disease[J]. Am J Clin Oncol, 1983, 6(3): 319-323.
4.	Karp JE, Sarkodee-Adoo CB. Therapy-related acute leukemia[J]. Clin Lab Med, 2000, 20(1): 71-81.
5.	Swerdlow, SH, Campo, E, Harris, NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues[M]. Lyon: IARC Press, 2008: 127-129.
6.	Pagano L , Pulsoni A , Tosti ME , et al. Acute lymphoblastic leukemia occurring as second malignancy: report of the GIMEMA archive of adult acute leukemia[J]. Br J Haematol, 1999, 106(4):.
7.	Ram R, Bonstein L, Gafter-Gvili A, et al. Rituximab-associated acute thrombocytopenia: an under-diagnosed phenomenon[J]. Am J Hematol, 2009, 84(4): 247-250.
8.	Hijiya N, Ness KK, Ribeiro RC. Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues[J]. Cancer, 2009, 115(1): 23-35.
9.	于虹, 付蓉, 阮二寶, 等. 急性非淋巴細胞白血病合并非霍奇金淋巴瘤3例報道[J]. 中國實用內科雜志, 2010, 30(12): 1131-1132.
10.	Schoch C, Kern W, Schnittger S, et al. Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML[J]. Leukemia, 2004, 18(1): 120.
11.	Rowley JD, Alimena G, Carson OM, et al. A collaborative study of the relationship of the morphologyic type of acute nonlymphocytic leukemia with patient age and karyotype[J]. Blood, 1982, 59(5): 1013-1022.
12.	Takeyama K, Seto M, Uike N, et al. Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytognetic features as well as prognostic factors[J]. Int J Hematol, 2000, 71(2): 144-152.
13.	McLaughlin P, Estey E, Glassman A, et al. Myelodysplasia and acute myeloid leukemia following therapy for indolent lymphoma with fludarabine, mitoxantrone, and dexamethasone (FND) plus rituximab and interferon alpha[J]. Blood, 2005, 105: 4573-4575.
14.	Martin-Salces M, Canales MA, de Paz R, et al. Treatment-related acute myeloid leukemia with 11q23 translocation following treatment with fludarabine, cyclophosphamide and rituximab[J]. Leuk Res, 2008, 32(1): 199-220.
15.	Larson RA. Therapy-related myeloid neoplasms[J]. Haematlogica, 2009, 94(4): 454-459 .
16.	Hoyle CF, de Bastos M, Wheatley K, et al. AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC’s 9th AML trial[J]. Br J haematol, 1989, 72(1): 45-53.
17.	展昭民, 陳德發, 吳紅舉, 等, 治療相關性白血病的治療[J]. 癌癥進展雜志, 2005, 3(2): 106-108.
18.	Ng A, Taylor GM, Eden OB. Treatment-related leukemia: a clinical and scientific challenge[J]. Cancer Treat Rev, 2000, 26(5): 377-391.
19.	Kroger N, Brand R, van Biezen A, et al. Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome[J]. Bone Marrow Transplant, 2006, 37(2): 183-189.
20.	-1040.

1. 　Armitage JO, Carbone PP, Connors JM, et al. Treatment-related myelodysplasia and acute leukemia in non-Hodgkin’s lymphoma patients[J]. J Clin Oncol, 2003, 21(5): 897-906.
2. 　Sacchi S, Marcheselli L, Bari A, et al, Secondary malignancies after treatment for indolent non-Hodgkin’s lymphoma, a 16-year follow-up study[J]. Hematologica, 2008, 93(3): 398-404.
3. 　Gomez GA, Friedman M, Reese P. Occurrence of acute nonlymphocytic leukemia in a prospective randomized study of treatment for Hodgkin’s disease[J]. Am J Clin Oncol, 1983, 6(3): 319-323.
4. 　Karp JE, Sarkodee-Adoo CB. Therapy-related acute leukemia[J]. Clin Lab Med, 2000, 20(1): 71-81.
5. 　Swerdlow, SH, Campo, E, Harris, NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues[M]. Lyon: IARC Press, 2008: 127-129.
6. 　Pagano L , Pulsoni A , Tosti ME , et al. Acute lymphoblastic leukemia occurring as second malignancy: report of the GIMEMA archive of adult acute leukemia[J]. Br J Haematol, 1999, 106(4):.
7. 　Ram R, Bonstein L, Gafter-Gvili A, et al. Rituximab-associated acute thrombocytopenia: an under-diagnosed phenomenon[J]. Am J Hematol, 2009, 84(4): 247-250.
8. 　Hijiya N, Ness KK, Ribeiro RC. Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues[J]. Cancer, 2009, 115(1): 23-35.
9. 　于虹, 付蓉, 阮二寶, 等. 急性非淋巴細胞白血病合并非霍奇金淋巴瘤3例報道[J]. 中國實用內科雜志, 2010, 30(12): 1131-1132.
10. 　Schoch C, Kern W, Schnittger S, et al. Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML[J]. Leukemia, 2004, 18(1): 120.
11. 　Rowley JD, Alimena G, Carson OM, et al. A collaborative study of the relationship of the morphologyic type of acute nonlymphocytic leukemia with patient age and karyotype[J]. Blood, 1982, 59(5): 1013-1022.
12. 　Takeyama K, Seto M, Uike N, et al. Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytognetic features as well as prognostic factors[J]. Int J Hematol, 2000, 71(2): 144-152.
13. 　McLaughlin P, Estey E, Glassman A, et al. Myelodysplasia and acute myeloid leukemia following therapy for indolent lymphoma with fludarabine, mitoxantrone, and dexamethasone (FND) plus rituximab and interferon alpha[J]. Blood, 2005, 105: 4573-4575.
14. 　Martin-Salces M, Canales MA, de Paz R, et al. Treatment-related acute myeloid leukemia with 11q23 translocation following treatment with fludarabine, cyclophosphamide and rituximab[J]. Leuk Res, 2008, 32(1): 199-220.
15. 　Larson RA. Therapy-related myeloid neoplasms[J]. Haematlogica, 2009, 94(4): 454-459 .
16. 　Hoyle CF, de Bastos M, Wheatley K, et al. AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC’s 9th AML trial[J]. Br J haematol, 1989, 72(1): 45-53.
17. 　展昭民, 陳德發, 吳紅舉, 等, 治療相關性白血病的治療[J]. 癌癥進展雜志, 2005, 3(2): 106-108.
18. 　Ng A, Taylor GM, Eden OB. Treatment-related leukemia: a clinical and scientific challenge[J]. Cancer Treat Rev, 2000, 26(5): 377-391.
19. 　Kroger N, Brand R, van Biezen A, et al. Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome[J]. Bone Marrow Transplant, 2006, 37(2): 183-189.
20. -1040.

《華西醫學》

非霍奇金淋巴瘤治療后繼發急性髓細胞白血病M6型一例

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《華西醫學》

非霍奇金淋巴瘤治療后繼發急性髓細胞白血病M6型一例

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