|LETTERS TO THE EDITOR
|Year : 2018 | Volume
| Issue : 3 | Page : 307-309
Autologous stem cell transplantation in elderly myeloma patients (>65 years): Single institutional experience
Rabindra K Jena1, Sudha Sethy1, Ashutosh Panigrahi1, Tribikram Panda2
1 Department of Clinical Hematology, S.C.B. Medical College and Hospital, Cuttack, Odisha, India
2 Department of Medicine, S.C.B. Medical College and Hospital, Cuttack, Odisha, India
|Date of Web Publication||28-Jan-2019|
Dr. Rabindra K Jena
Department of Clinical Hematology, S.C.B. Medical College and Hospital, Cuttack, Odisha
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Jena RK, Sethy S, Panigrahi A, Panda T. Autologous stem cell transplantation in elderly myeloma patients (>65 years): Single institutional experience. Indian J Cancer 2018;55:307-9
|How to cite this URL:|
Jena RK, Sethy S, Panigrahi A, Panda T. Autologous stem cell transplantation in elderly myeloma patients (>65 years): Single institutional experience. Indian J Cancer [serial online] 2018 [cited 2019 Sep 23];55:307-9. Available from: http://www.indianjcancer.com/text.asp?2018/55/3/307/250882
High-dose chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) has remained the standard of care for multiple myeloma for the last three decades as it gives a better survival advantage compared to CT alone. Selection of patients for ASCT in the European Union has been limited to patients less than 65 years, whereas in the United States elderly patients (>65 years) are still considered after evaluating biological age and bone marrow transplantation (BMT) comorbidity index., Like European Union, BMT centers in India consider elderly patients not suitable for ASCT. Here, we present five elderly cases (>65 years) who have undergone successful ASCT and are performing well after day +100.
The baseline characteristics and disease profile of five cases are depicted in [Table 1]. The mean age of our patients was 69.2 years. All our patients were evaluated with detailed history, general and systemic examinations, hematological and biochemical parameters, bone marrow study, serum protein electrophoresis and immunofixation, estimation of serum free light chains (FLCs) ratio, urine analysis, and 24 h urinary protein estimation. There was no significant associated comorbidity among our patients [except for cases 2 and 3 as shown in [Table 1].
All cases received appropriate induction CT as depicted in [Table 1]. After achievement of satisfactory response (≥ very good partial response), detail pretransplant evaluation was done in all cases. Case no 2 had renal impairment with clearance of 24.7 mL/min, while others had no abnormalities. All cases were well selected with performance score ≥90 (Karnofsky scale). Stem cell mobilization was done with Granulocyte Colony Stimulating Factor (G-CSF), 10μg/kg/day with/without plerixafor. Peripheral blood stem cell was collected by apheresis and the yield of each case with CD34 count is depicted in [Table 1].
All were conditioned with high-dose melphalan (MPL) (200 mg/m2) except for case 2 where dose was adjusted (140 mg/m2) following standard procedures. The major conditioning-related toxicities [as per Common Terminology Criteria for Adverse Events (CTCAE 4.0)] for each case are shown in [Table 2].
After conditioning, the collected stem cells were infused. Posttransplant, G-CSF (5μg/kg/day) was given from day + 5 till engraftment. Platelet and red cell support were administered when ever needed. Levofloxacin, acyclovir, and fluconazole were used as infection prophylaxis along with other supportive treatment. The engraftment duration, length of hospital stay, and disease status at D+100 are shown in [Table 2]. Subsequently, (from D+101) all cases received intravenous bortezomib, 1.3 mg/m2 subcutaneously every 2 weeks as maintenance till progression or unacceptable toxicities.
Clinical trials of ASCT have been mostly undertaken in patients younger than 65 years of age and reports of ASCT performed in elderly patients are hardly available as transplant-related morbidity and mortality are high in the latter. Though geriatric assessment and HSCT (Hematopoietic Stem Cell Transplantation) comorbidity index has been included in pretransplant workup, we have not used it. We selected our elderly myeloma patients, for ASCT on basis of preserved organ function, minimal comorbidity and good performance status as per Karnofsky scale.
Case no 1, 4 achieved CR (Complete response) with two drug induction CT. Case nos. 3 and 5, initially not willing for ASCT achieved CR with three drug induction CT, i.e., 9 × MPL and 5 × Melphalan, Prednisolone, Velcade/Bortezomib(MPV), respectively. Both the cases were lost to follow-up, relapsed and reachieved CR with CT of 6×Bortezomib, Dexamethasone (BD) and 3 × BD, respectively [Table 1]. With this regimen all cases achieved CR before ASCT without significant treatment-related toxicity.
Plerixafor has been demonstrated to be an effective strategy for mobilization in patients after lenalidomide-based initial therapy and can overcome the negative effects of most predictors of poor mobilization., Plerixafor was administered in cases 2 and 5 because of low CD34 count after G-CSF and the CD34count increased significantly in both the cases [Table 2]. Adequate stem cell mobilization was achieved in all the cases.
For last 30 years high-dose MPL (200 mg/m2) is being used for conditioning following a randomized trial conducted by the IFM (Intergroupe Francophone du Myeloma). Similarly, we have used high-dose MPL in our patients without any significant morbidity or mortality which may be partly due to preserved organ function. In retrospective analysis, Qazilbash et al. has reported the safety of high-dose MPL (200 mg/m2) vis-à -vis 180 mg/m2, while one recent prospective multicentric study have documented the safety and better efficacy of MPL (200 mg/m2) in comparison to dose of 140 mg/m2 in elderly myeloma patients (>65 years). Hence, MPL 200 mg/m2 is feasible in selected elderly patients.
We infused all the collected stem cells (mean stem cell dose was 8.36 × 106/kg). No adverse event has been encountered with the use of higher CD34+ dose. All our patients achieved sCR (Stringent complete response) on D+100 (post-ASCT) and received maintenance bortezomib after day + 100 of ASCT without documentation of any significant morbidity.
This unique experience, although on a small cohort of patients, suggests that stem cell mobilization, conditioning regimen, engraftment, and outcome of ASCT in selected elderly patients are comparable with that of younger group.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al
. Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients. Leukemia 2014;28:1122-8.
Belotti A, Ribolla R, Crippa C, Cattaneo C, Morello E, Orlando V, et al
. Bortezomib-Based Induction Regimen Followed By Autologous Stem Cell Transplantation (ASCT) after Conditioning with MEL200 Is Highly Effective and Well Tolerated in Elderly. Multiple Myeloma (MM) Patients up to the Age of 75 Years. Blood 2017;130.
Hailemichael H, Kaufman JL, Flowers CR, Waller EK, Lechowicz MJ, Langston A, et al
. Do Elderly Myeloma Patients Benefit From High Dose Therapy (HDT) and Autologous Stem Cell Transplant (ASCT)?: A Comparative Survival Analysis using SEER Registry. Blood 2012;120:2072.
Kumar SK, Mikhael J, Laplant B, Lacy MQ, Buadi FK, Dingli D, et al
. Phase 2 trial of intravenously administered plerixafor for stem cell mobilization in patients with multiple myeloma following lenalidomide-based initial therapy. Bone Marrow Transplant 2014;49:201-5.
Lanza F, Lemoli RM, Olivieri A, Laszlo D, Martino M, Specchia G, et al
. Factors affecting successful mobilization with plerixafor: An Italian prospective survey in 215 patients with multiple myeloma and lymphoma. Transfusion 2014;54:331-9.
Moreau P, Attal M and Harousseau J. New developments in conditioning regimens before auto-SCT in multiple myeloma. Bone Marrow Transplant 2011;46:911-5.
Qazilbash MH, Saliba RM, Hosing C, Mendoza F, Qureshi SR, Weber DM, et al
. Autologous stem cell transplantation is safe and feasible in elderly patients with multiple myeloma. Bone Marrow Transplant 2007;39:279-83.
Garderet L, Beohou E, Caillot D, Stoppa AM, Touzeau C, Chretien ML, et al
. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: A prospective multicenter study. Haematologica 2016;101:1390-7.
[Table 1], [Table 2]