INFECTION EVENTS IN MULTIPLE MYELOMA DURING THE EARLY PERIOD OF AUTOLOGOUS STEM CELL TRANSPLANTATION

Öz

Objective: Multiple myeloma (MM) patients have a high risk of developing infections. In this study, we documented the infec tion events in patients with MM who underwent autologous hae matopoietic stem cell transplantation (AHSCT). Material and Method: Patients who received an induction regi men and underwent AHSCT were enrolled in the study. Routine antimicrobial prophylaxis was not given. Infection treatment was performed in accordance with the febrile neutropenia guidelines. Result: Between May 2007 and November 2016, 150 patients with MM underwent AHSCT. The median age was 51.7±7.2 years, and the male-to-female ratio was 84/66. Nearly all patients developed fever. The median time from the HSCT day to the first fever episode was 7.4±2.8 days. Pneumonia and oropharyngeal candidiasis were frequently associated with fever. Blood and urine culture positivity was 18.6% and 20%, respectively. The neutropenia duration was not associated with culture positivity but proved to be longer in patients who had received two types of induction regimen (8.4±3.7 vs. 7.4±2.3 days, p=0.056). The mortality rate in the first 100 days was 0.6%, which was similar to the results of other experienced centers. Conclusion: Our study encompassed the period when the in duction regimen included combinations of chemotherapy, and novel agents were used after chemotherapy refractoriness or for improvement in response quality. In relation to this, most patients received second-line induction therapy. The infection events were manageable, and patients showed acceptable out comes and a very low early mortality rate.

Anahtar Kelimeler

• Multiple myeloma
• autologous haematopoietic stem cell transplantation
• infection
• febrile neutropenia

MULTİPL MİYELOMDA OTOLOG KÖK HÜCRE TRANSPLANTASYONUNUN ERKEN DÖNEMİNDE ENFEKSİYON OLAYLARI

Öz

Amaç: Multipl miyelom (MM) hastalarında enfeksiyon gelişme riski yüksektir. Bu çalışmada, otolog hematopoetik kök hücre nakli (OHKHN) yapılan MM hastalarında enfeksiyon olayları derlemiştir. Gereç ve Yöntem: İndüksiyon rejimi ardından OHKHN uygula nan MM hastaları çalışmaya dahil edilmiştir. Rutin antimikrobiyal profilaksi uygulanmamıştır. Enfeksiyon tedavileri febril nötropeni kılavuzlarına paralel yapılmıştır. Bulgular: Mayıs 2007 ve Kasım 2016 tarihleri arasında toplam 150 MM hastasına OHKHN uygulandı. Ortanca yaş 51,7±7,2 yıl ve erkek/kadın oranı 84/66 idi. Hastaların neredeyse tama mında ateş gelişti. HKHN gününden ilk ateş atağına kadar geçen süre ortanca 7,4±2,8 gündü. Ateşle en sık ilişkili en feksiyonlar pnömoni ve orofarengeal kandidiyazis idi. Kan ve idrar kültürü pozitifliği sırasıyla %18,6 ve %20 olarak bulundu. Nötropeni süresi kültür pozitifliği ile ilişkili değildi, ancak iki tip indüksiyon rejimi alan hastalarda nötropeninin daha uzun sürdüğü görüldü (8,4±3,7 vs, 7,4±2,3 gün, p=0,056). İlk 100 günde mortalite oranı %0,6 olup diğer deneyimli merkezlerin sonuçlarına benzerdi. Sonuç: Çalışmamız, indüksiyon rejiminin kemoterapi kombinas yonları ile yapıldığı ve yeni ajanların kemoterapi refrakterliğin den sonra veya yanıt kalitesinde iyileşme için kullanıldığı dönemi kapsamaktadır. Bununla bağlantılı olarak, hastaların çoğu ikinci basamak indüksiyon almıştır. Buna rağmen, hastalar çok düşük erken mortalite oranı ile kabul edilebilir bir sonuç göstermiştir.

Anahtar Kelimeler

• Multipl miyelom
• otolog hematopoietik kök hücre nakli
• enfeksiyon
• febril nötropeni

Kaynakça

1. 1. Blimark C, Holmberg E, Mellqvist UH, Landgren O, Björkholm M, Hultcrantz M, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica 2015;100(1):107-13. [CrossRef] google scholar
2. 2. Huang W, Wei X, Wei Q, Wei Y, Feng R. Partial immunoparesis contributes to risk of early infections in patients with multiple myeloma. Transl Cancer Res 2021;10(12):5258-66. [CrossRef] google scholar
3. 3. Bladé J, Rosiñol L. Renal, hematologic and infectious complications in multiple myeloma. Best Pract Res Clin Haematol 2005;18(4):635-52. [CrossRef] google scholar
4. 4. Valković T, Gačić V, Ivandić J, Petrov B, Dobrila-Dintinjana R, Dadić-Hero E, et al. Infections in Hospitalised Patients with Multiple Myeloma: Main Characteristics and Risk Factors. Turk J Haematol 2015;32(3):234-42. [CrossRef] google scholar
5. 5. Hyun SY, Han SH, Kim S-J, Jang JE, Kim Y, Cho H, et al. Pretreatment lymphopenia, poor performance status, and early courses of therapy are risk factors for severe bacterial infection in patients with multiple myeloma during treatment with bortezomib-based regimens. J Korean Med Sci 2016;31(4):510-8. [CrossRef] google scholar
6. 6. Teh BW, Harrison SJ, Worth LJ, Thursky KA, Slavin MA. Infection risk with immunomodulatory and proteasome inhibitor-based therapies across treatment phases for multiple myeloma: A systematic review and meta-analysis. Eur J Cancer 2016;67:21-37. [CrossRef] google scholar
7. 7. Teh BW, Harrison SJ, Worth LJ, Spelman T, Thursky KA, Slavin MA. Risks, severity and timing of infections in patients with multiple myeloma: a longitudinal cohort study in the era of immunomodulatory drug therapy. Br J Haematol 2015;171(1):100-8. [CrossRef] google scholar
8. 8. Dimopoulos MA, Moreau P, Terpos E, Mateos M-V, Zweegman S, Cook G, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2021;32(3):309-22. [CrossRef] google scholar

9. 9. Nieto MJ, Hedjar A, Locke M, Caro J, Saif MW. Analysis of Updates in Multiple Myeloma Treatment and Management. J Clin Haematol 2023;4(1):35-42. [CrossRef] google scholar
10. 10. Carreras E, Dufour C, Mohty M, Kröger N, editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th ed. Cham (CH): Springer; 2019. [CrossRef] google scholar
11. 11. NCCN Guidelines Version 3.2022 Prevention and Treatment of Cancer-Related Infections https://www.nccn.org/ professionals/physician_gls/pdf/infections.pdf google scholar
12. 12. Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, et al; ESMO Guidelines Committee. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol 2016;27(suppl 5):v111-8. [CrossRef] google scholar
13. 13. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drugresistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268-81. [CrossRef] google scholar
14. 14. Gil L, Styczynski J, Komarnicki M. Infectious complication in 314 patients after high-dose therapy and autologous hematopoietic stem cell transplantation: risk factors analysis and outcome. Infection 2007;35(6):421-7. [CrossRef] google scholar
15. 15. Celebi H, Akan H, Akçaglayan E, Ustün C, Arat M. Febrile neutropenia in allogeneic and autologous peripheral blood stem cell transplantation and conventional chemotherapy for malignancies. Bone Marrow Transplant 2000;26(2):211-4. [CrossRef] google scholar
16. 16. Nesher L, Rolston KVI. Febrile Neutropenia in Transplant Recipients. Principles and Practice of Transplant Infectious Diseases 2018;8:185-98. [CrossRef] google scholar
17. 17. Hsu P, Lin TW, Gau JP, Yu YB, Hsiao LT, Tzeng CH, et al. Risk of Early Mortality in Patients With Newly Diagnosed Multiple Myeloma. Medicine (Baltimore) 2015;94(50):e2305. [CrossRef] google scholar
18. 18. Grant SJ, Wildes TM, Rosko AE, Silberstein J, Giri S. A real-world data analysis of predictors of early mortality after a diagnosis of multiple myeloma. Cancer 2023;129(13):2023-34. [CrossRef] google scholar
19. 19. Zahid MF, Ali N, Nasir M, Baig MH, Iftikhar M, Mahmood SUB, et al. Infections in patients with multiple myeloma treated with conventional chemotherapy: a single-center, 10-year experience in Pakistan. Hematol Transfus Cell Ther 2019;41:292-7. [CrossRef] google scholar
20. 20. Brioli A, Klaus M, Sayer H, Scholl S, Ernst T, Hilgendorf I, et al. The risk of infections in multiple myeloma before and after the advent of novel agents: a 12-year survey. Ann Hematol 2019;98:713-22. [CrossRef] google scholar
21. 21. Chen M, Zhao Y, Xu C, Wang X, Zhang X, Mao B. Immunomodulatory drugs and the risk of serious infection in multiple myeloma: systematic review and meta-analysis of randomized and observational studies. Ann Hematol 2018;97:925-44. [CrossRef] google scholar
22. 22. Balmaceda N, Aziz M, Chandrasekar VT, McClune B, Kambhampati S, Shune L, et al. Infection risks in multiple myeloma: a systematic review and meta-analysis of randomized trials from 2015 to 2019. BMC Cancer 2021;21(1):1-11. [CrossRef] google scholar
23. 23. Lin C, Shen H, Zhou S, Liu M, Xu A, Huang S, et al. Assessment of infection in newly diagnosed multiple myeloma patients: risk factors and main characteristics. BMC Infect Dis 2020;20(1):1-11. [CrossRef] google scholar
24. 24. Marchesi F, Pimpinelli F, Gumenyuk S, Renzi D, Palombi F, Pisani F, et al. Cytomegalovirus reactivation after autologous stem cell transplantation in myeloma and lymphoma patients: a single-center study. World J Transplant 2015;5(3):129-36. [CrossRef] google scholar
25. 25. Raje NS, Anaissie E, Kumar SK, Lonial S, Martin T, Gertz MA, et al. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol 2022;9(2):e143-61. [CrossRef] google scholar
26. 26. Lim C, Sinha P, Harrison SJ, Quach H, Slavin MA, Teh BW. Low rates of invasive fungal disease in patients with multiple myeloma managed with new generation therapies: Results from a multi-centre cohort study. Mycoses 2021;64(1):30-4. [CrossRef] google scholar