Clofarabine, cyclophosphamide, and etoposide (CLOVE) in adult patients with relapsed/refractory acute T-cell lymphoblastic leukemia: single-center experience
Öz
Purpose: Clofarabine is a second-generation purine analog that inhibits DNA synthesis. It is used as an effective new agent in relapsed refractory acute leukemia. We aimed to report our single center experience about CLOVE protocol as a clofarabine-based regimen in patients with relapsed or refractory T-cell acute lymphoblastic leukemia.
Materials and Methods: Thirteen patients with relapsed or resistant T-cell acute lymphoblastic leukemia were included in this study. Patients were administered clofarabine (40 mg/m2/day), etoposide (100 mg/m2/day), and cyclophosphamide (440 mg/m2/day) (5 days chemotherapy). The patients' data were reviewed retrospectively, the demographic and clinical characteristics of patients were recorded.
Results: The patients' median age was 47, and 77% (n:10) of them were male. The median number of chemotherapy regimens they received before clofarabine was 3. Of the patients, 54% (n=7) presented with relapse, and 46% (n=6) with refractory disease. Hematological side effects were observed in all patients during treatment, and 4 (31%) patients were complicated by febrile neutropenia. Other side effects were hepatotoxicity 39%, skin reaction 2%, nausea 54%, and mucositis 31%. Three (23%) patients were unresponsive to treatment. A response was obtained in 10 (77%) patients. Allogeneic stem cell transplantation was performed in 4 of 5 patients with complete response. The median follow-up time after CLOVE was 2.3 (0.69-26.02) months. The median estimated survival time was 21.04 ± 3.88 (95%CI: 13.43 -28.64) months. Overall survival was 85.7% at three months and 57.1% at one year. Three patients were alive at the end of our study.
Conclusion: The combination of clofarabine, etoposide, and cyclophosphamide (CLOVE) appears to be successful in achieving a response in relapsing or resistant acute leukemia. However, more effective regimens are still needed.
Anahtar Kelimeler
Clofarabine relapsed/resistant leukemia T-cell acute lymphoblastic leukemia
Kaynakça
- Marks DI, Rowntree C. Management of adults with T-cell lymphoblastic leukemia. Blood. 2017;129:1134-42.
- Patel AA, Thomas J, Rojek AE, Stock W. Biology and Treatment Paradigms in T Cell Acute Lymphoblastic Leukemia in Older Adolescents and Adults. Curr Treat Options Oncol. 2020;21:57.
- Duval M, Klein JP, He W, Cahn J-Y, Cairo M, Camitta BM et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28:3730-8.
- Camera A, Annino L, Chiurazzi F, Fazi P, Cascavilla N, Fabbiano F et al. GIMEMA ALL - Rescue 97: a salvage strategy for primary refractory or relapsed adult acute lymphoblastic leukemia. Haematologica. 2004;89:145-53.
- Jeha S, Gandhi V, Chan KW, McDonald L, Ramirez I, Madden R et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004;103:784-9.
- Jeha S, Gaynon PS, Razzouk BI, Franklin J, Kadota R, Shen V et al. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006;24:1917-23.
- Suzuki T, Yamauchi T, Ando K, Nagai T, Kakihana K, Miyata Y et al. Phase I study of clofarabine in adult patients with acute myeloid leukemia in Japan. Jpn J Clin Oncol. 2013;43:1177-83.
- Zhenchuk A, Lotfi K, Juliusson G, Albertioni F. Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009;78:1351-9.
- Jeha S, Gandhi V, Chan KW, McDonald L, Ramirez I, Madden R et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004;103:784-9.
- Kantarjian HM, Gandhi V, Kozuch P, Faderl S, Giles F, Cortes J et al. Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers. J Clin Oncol. 2003;21:1167-73.
- Hijiya N, Gaynon P, Barry E, Silverman L, Thomson B, Chu R et al. A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia. Leukemia. 2009;23:2259-64.
- Miano M, Pistorio A, Putti MC, Dufour C, Messina C, Barisone E et al. Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients. Leuk Lymphoma. 2012;53:1693-8.
- Micalizzi C, Parasole R, Putti MC, Luciani M, Banov L, Petruzziello F et al. Clofarabine in Combination with Etoposide and Cyclophosphamide (CLOVE) in Pediatric Patients with Relapsed Acute Leukemia: 4 Italian Pediatric AIEOP Centers' Experience. 2008;112:3953.
- Saito T, Hatta Y, Hayakawa F, Takahashi T, Hagihara M, Iida H et al. Combination of clofarabine, etoposide, and cyclophosphamide in adult relapsed/refractory acute lymphoblastic leukemia: a phase 1/2 dose-escalation study by the Japan Adult Leukemia Study Group. Int J Hematol. 2021;113:395-403.
- Barba P, Sampol A, Calbacho M, Gonzalez J, Serrano J, Martínez-Sánchez P et al. Clofarabine-based chemotherapy for relapsed/refractory adult acute lymphoblastic leukemia and lymphoblastic lymphoma. The Spanish experience. Am J Hematol. 2012;87:631-4.
- Cheson BD, Vena DA, Foss FM, Sorensen JM. Neurotoxicity of purine analogs: a review. J Clin Oncol. 1994;12:2216-28.
Relaps/refrakter T hücreli akut lenfoblastik lösemili erişkin hastalarda klofarabin, siklofosfamid, etoposid (CLOVE): tek merkez deneyimi
Öz
Amaç: Klofarabin, DNA sentezini inhibe eden ikinci nesil bir pürin analoğudur. Nükseden, dirençli akut lösemide etkili yeni bir ajan olarak kullanılır. Nükseden veya dirençli T hücreli akut lenfoblastik lösemili hastalarda klofarabin bazlı bir rejim olarak CLOVE protokolü ile ilgili tek merkez deneyimimizi bildirmeyi amaçladık.
Gereç ve Yöntem: Nükseden veya dirençli T hücreli akut lenfoblastik lösemili 13 hasta bu çalışmaya dahil edildi. Hastalara klofarabin (40 mg/m2/gün), etoposid (100 mg/m2/gün) ve siklofosfamid (440 mg/m2/gün) (5 gün süre ile) uygulandı. Hastaların verileri retrospektif olarak incelendi, hastaların demografik ve klinik özellikleri kaydedildi.
Bulgular: Hastaların ortanca yaşı 47 olup, %77'si (n:10) erkekti. Klofarabinden önce aldıkları ortanca kemoterapi rejimi sayısı 3 idi. Hastaların %54'ü (n=7) nüks, %46'sı (n=6) dirençli hastalık ile başvurdu. Tedavi sırasında tüm hastalarda hematolojik yan etkiler gözlendi ve 4 (%31) hastada febril nötropeni gelişti. Diğer yan etkiler %39 hepatotoksisite, %2 cilt reaksiyonu, %54 bulantı ve %31 mukozit idi. Üç (%23) hasta tedaviye yanıtsızdı. On (%77) hastada tedaviye yanıt (tam yanıt ve kısmi yanıt) alındı. Tam yanıt alınan 5 hastanın 4'üne allojenik kök hücre nakli yapıldı. CLOVE sonrası ortanca takip süresi 2,3 (0,69-26,02) aydı. Ortanca tahmini hayatta kalma süresi 21,04 ± 3,88 (%95 GA: 13,43 -28,64) aydı. Genel sağkalım üç ayda %85.7 ve bir yılda %57.1 idi. Çalışmamızın sonunda üç hasta hayattaydı.
Sonuç: Klofarabin, etoposid ve siklofosfamid (CLOVE) kombinasyonu, tekrarlayan veya dirençli akut lösemide yanıt elde etmede başarılı görünmektedir. Bununla birlikte, daha etkili rejimlere hala ihtiyaç vardır.
Anahtar Kelimeler
Klofarabin tekrarlayan/dirençli lösemi T-hücreli akut lenfoblastik lösemi
Kaynakça
- Marks DI, Rowntree C. Management of adults with T-cell lymphoblastic leukemia. Blood. 2017;129:1134-42.
- Patel AA, Thomas J, Rojek AE, Stock W. Biology and Treatment Paradigms in T Cell Acute Lymphoblastic Leukemia in Older Adolescents and Adults. Curr Treat Options Oncol. 2020;21:57.
- Duval M, Klein JP, He W, Cahn J-Y, Cairo M, Camitta BM et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28:3730-8.
- Camera A, Annino L, Chiurazzi F, Fazi P, Cascavilla N, Fabbiano F et al. GIMEMA ALL - Rescue 97: a salvage strategy for primary refractory or relapsed adult acute lymphoblastic leukemia. Haematologica. 2004;89:145-53.
- Jeha S, Gandhi V, Chan KW, McDonald L, Ramirez I, Madden R et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004;103:784-9.
- Jeha S, Gaynon PS, Razzouk BI, Franklin J, Kadota R, Shen V et al. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006;24:1917-23.
- Suzuki T, Yamauchi T, Ando K, Nagai T, Kakihana K, Miyata Y et al. Phase I study of clofarabine in adult patients with acute myeloid leukemia in Japan. Jpn J Clin Oncol. 2013;43:1177-83.
- Zhenchuk A, Lotfi K, Juliusson G, Albertioni F. Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009;78:1351-9.
- Jeha S, Gandhi V, Chan KW, McDonald L, Ramirez I, Madden R et al. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004;103:784-9.
- Kantarjian HM, Gandhi V, Kozuch P, Faderl S, Giles F, Cortes J et al. Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers. J Clin Oncol. 2003;21:1167-73.
- Hijiya N, Gaynon P, Barry E, Silverman L, Thomson B, Chu R et al. A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia. Leukemia. 2009;23:2259-64.
- Miano M, Pistorio A, Putti MC, Dufour C, Messina C, Barisone E et al. Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients. Leuk Lymphoma. 2012;53:1693-8.
- Micalizzi C, Parasole R, Putti MC, Luciani M, Banov L, Petruzziello F et al. Clofarabine in Combination with Etoposide and Cyclophosphamide (CLOVE) in Pediatric Patients with Relapsed Acute Leukemia: 4 Italian Pediatric AIEOP Centers' Experience. 2008;112:3953.
- Saito T, Hatta Y, Hayakawa F, Takahashi T, Hagihara M, Iida H et al. Combination of clofarabine, etoposide, and cyclophosphamide in adult relapsed/refractory acute lymphoblastic leukemia: a phase 1/2 dose-escalation study by the Japan Adult Leukemia Study Group. Int J Hematol. 2021;113:395-403.
- Barba P, Sampol A, Calbacho M, Gonzalez J, Serrano J, Martínez-Sánchez P et al. Clofarabine-based chemotherapy for relapsed/refractory adult acute lymphoblastic leukemia and lymphoblastic lymphoma. The Spanish experience. Am J Hematol. 2012;87:631-4.
- Cheson BD, Vena DA, Foss FM, Sorensen JM. Neurotoxicity of purine analogs: a review. J Clin Oncol. 1994;12:2216-28.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma |
| Yazarlar | |
| Erken Görünüm Tarihi | 10 Temmuz 2023 |
| Yayımlanma Tarihi | 2 Temmuz 2023 |
| Kabul Tarihi | 25 Mayıs 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 48 Sayı: 2 |
