Pegfilgrastim versus filgrastim to accelerate hematopoietic recovery after high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma

Abstract Introduction: For younger patients under 65 years of age, induction followed by high-dose chemotherapy with autologous stem cell transplantation (ASCT) is the standard treatment in multiple myeloma (MM). There is limited experience with non-cryopreserved autologous hematopoietic stem cell transplantation. We evaluated the efficacy and safety of non-cryopreserved storage of ASCT in patients undergoing ASCT for MM. Patients and methods: Autologous stem cell was mobilized using G-CSF alone (10 µg/kg/day for 5 days). Leukapheresis to harvest stem cells were performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at +4°C until reinfusion on day 0. The conditioning regimen consisted of melphalan 200 mg/m2 in all patients. Results: From May 2009 to December 2013, 134 patients with MM were treated in our center in Oran. The median age at ASCT was 55 years (range; 27-67). There were 80 males and 54 females. The median harvested CD34+ cell count was 3,5x106/kg (range; 1, 22 to 13, 24). All patients had engraftment on the median of day 10 (range; 7 to 17) and platelet transfusion independence on the median of day 13 (range; 9 to 24). There was no graft failure. Mucositis grade 3/4 was seen in 68% patients. Transplant related mortality at 100 days was 2.9%. The overall response to transplant was 92%. In the 130 evaluable patients, the median post-transplant overall survival had not been reached. The estimated overall survival at 75 months was 63% with 95% confidence interval and the median post-transplant disease free Survival was 35 months (0.05%). 93 (72%) patients are alive and 75 (81%) without disease activity after a median follow-up of 35 months (range; 3 to 75). Discussion: We conclude that high dose chemotherapy and autologous transplant with non cryopreserved ASCT is a simple, effective and safe method for MM with equivalent results, and that cryopreservation is not necessary in the treatment of MM under our work conditions in developing countries Disclosures No relevant conflicts of interest to declare.

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The Importance of the Number of Transplanted Cells with Dipeptidyl Peptidase-4 Expression on the Hematopoietic Recovery and Lymphocyte Reconstitution in Patients with Multiple Myeloma after Autologous Hematopoietic Stem-Cell Transplantation

Blood ◽

10.1182/blood.v126.23.5415.5415 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5415-5415

Author(s):

Anna Kopinska ◽

Malgorzata Krawczyk-Kulis ◽

Joanna Dziaczkowska-Suszek ◽

Katarzyna Bieszczad ◽

Krystyna Jagoda ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem ◽

Dipeptidyl Peptidase 4 ◽

Hematopoietic Recovery ◽

Cd34 Cells

Abstract Introduction Autologous hematopoietic stem cell transplantation (AHSCT) remains the treatment of choice in multiple myeloma (MM) patients (pts). In earlier research it has been suggested that the expression of dipeptidyl peptidase-4 (DPP4, CD26) influences both the homing and lymphocyte reconstitution after AHSCT in pts with lymphoproliferative neoplasms. The aim of the study is to investigate the effect of transplanted CD26 positive cells of the hematopoietic recovery and lymphocyte reconstitution in MM pts after AHSCT. Patients and methods Forty eight pts with MM with median age 56 (range 21-76) were undergoing AHSCT in our center in years 2011-2013. Conditioning regimen was Melphalan 200. Number of all CD26+ cells, CD26+ lymphocytes, CD26+ monocytes and CD26+ and CD34+ cells were measured in harvested material. Number of lymphocyte's subpopulations (all lymphocytes CD3+, helpers CD3+CD4+, suppressors CD3+CD8+, natural killer (NK) CD3-CD16+CD56+, cytotoxic NK CD3+CD16+CD56+, lymphocytes B CD3-CD19+) were measured in peripheral blood during regeneration period after AHSCT. In both flow cytometry was used. The hematopoietic regeneration was measured as following: the day of white blood cells' regeneration when WBC count reached >1,0x109/L, the day of granulocytes' regeneration when ANC >0,5x109/L and the day of platelets' regeneration when PLT >20x109/L. Results All pts successfully engrafted. The results of AHSCT are shown in table nr 1. Table 1. The number of transplanted cells and regeneration during the procedure AHSCT in pts with MM. Parameter Median Range Mean Standard deviation Number of transplanted WBCx108/kg b.w. 4,26 0,73-18,8 5,43 4,36 Number of transplanted CD34+cells x106/kg b.w. 3,36 2,2-8,2 3,52 1,28 Number of transplanted CD26+ lymphocytes [109/L] 46,5 9-148 53,6 30,8 Number of transplanted CD26+ monocytes [109/L] 3,65 0-82 8,03 13,05 Number of all transplanted CD26+ cells [109/L] 50,42 9,6-213 62,5 23,2 Regeneration WBC >1x109/L (day) 13 10-20 13 2,64 ANC >0.5x109/L (day) 13 9-20 13,3 2,16 PLT >20x109/L (day) 14 11-20 14,1 2,18 As regards regeneration of hematopoietic cells after AHSCT it was shown that a higher number of transplanted CD26+ monocytes improves the reconstitution of suppressor (p=0,019) and NK lymphocytes (p=0,0237). A higher number of all transplanted CD26+ lymphocytes has a positive impact of the reconstitution of suppressor lymphocytes (p=0,0054), whereas a higher number of all transplanted the CD26+ cells improves the regeneration of cytotoxic NK (p=0,0126) and helper lymphocytes (p=0,0261). There were no confirmed adverse effects of the number of CD26+ cells on the hematopoietic regeneration0 and lymphocytes B reconstitution after AHSCT. Discussion Our research shows that the number of transplanted CD26-positive cells may improve immune reconstitution after AHSCT in patients with multiple myeloma, which was not clearly demonstrated before. As is well known faster lymphocyte reconstitution after AHSCT is associated with improved patient survival. Therefore, the greater the number of transplanted autologous CD26-positive cells may be associated with improved survival, which, however, needs further investigation. Disclosures No relevant conflicts of interest to declare.

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Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma without Cryopreservation

Bone Marrow Research ◽

10.1155/2012/917361 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Khalid Ahmed Al-Anazi

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

High Dose ◽

Hematopoietic Stem ◽

Conditioning Therapy

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is considered the standard of care for multiple myeloma patients who are eligible for transplantation. The process of autografting comprises the following steps: control of the primary disease by using a certain induction therapeutic protocol, mobilization of stem cells, collection of mobilized stem cells by apheresis, cryopreservation of the apheresis product, administration of high-dose pretransplant conditioning therapy, and finally infusion of the cryopreserved stem cells after thawing. However, in cancer centers that treat patients with multiple myeloma and have transplantation capabilities but lack or are in the process of acquiring cryopreservation facilities, alternatively noncryopreserved autologous stem cell therapy has been performed with remarkable success as the pretransplant conditioning therapy is usually brief.

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Long term follow-up report of cardiac toxicity in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation

Radiology and Oncology ◽

10.2478/raon-2013-0019 ◽

2013 ◽

Vol 47 (2) ◽

pp. 161-165 ◽

Cited By ~ 6

Author(s):

Mirta Kozelj ◽

Samo Zver ◽

Vesna Zadnik

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Side Effects ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

High Dose ◽

Hematopoietic Stem

Background. Tandem autologous hematopoietic stem cell transplantation (ta-HSCT) is a standard treatment for multiple myeloma (MM). Patients receive a high-dose cyclophosphamide (CY), followed by two myeloablative cycles of melphalan (MEL). There are scarce data about long term cardiotoxicity. Patients and methods. We studied 12 patients (62.25 ± 8.55 years) six years after the completion of MM treatment with ta-HCST. Late cardiotoxic effects were evaluated clinically and echocardiographically. Results. None of the patients developed clinical signs of heart failure, all were in sinus rhythm and NT-pro BNP concentration was elevated (778 ± 902.76 pg/mL). The left ventricular (LV) size remained normal. The LV ejection fraction did not decrease (73.75 ± 5.67%, 69.27 ± 6.13%, p = NS). The LV diastolic function parameters (E, A, ratio E/A and A/a) did not change significantly. In tissue Doppler parameters we observed a nonsignificant decrease in Em (10.26 ± 2.63 cm/s, 7.57 ± 1.43 cm/s) and Sm velocities (8.7 ± 0.87 cm/s, 7.14 ± 1.17 cm/s, p = NS). The E/Em values were in an abnormal range (8.66 ± 1.05, 10.55 ± 2.03). Conclusions. The treatment of MM with ta-HSCT, during which patients receive a high dose CY followed by two myeloablative cycles of MEL, causes mild, chronic, partially reversible and clinically silent cardiotoxic side-effects. However, ta-HSCT in patients with MM is a safe regarding cardiotoxic side effects, but, because of increasing life expectancy needs long term attention.

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