An Effective Hematopoietic Stem Cell Mobilization Algorithm for Adding Plerixafor to G-CSF for Multiple Myeloma Patients Undergoing Autologous Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4389-4389 ◽  
Author(s):  
Justin LaPorte ◽  
Scott R. Solomon ◽  
Asad Bashey ◽  
H. Kent Holland ◽  
Lawrence E. Morris ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Cell Count ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Small Sample ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
The Absolute

Abstract Abstract 4389 Background: Autologous hematopoietic stem cell transplantation (ASCT) has become an integral part of the treatment for multiple myeloma (MM). In addition, it is standard practice to collect enough stem cells for more than one transplant. Therefore, it is critical to have an effective mobilization strategy in order to efficiently collect sufficient numbers of CD34+ cells. Administering granulocyte-colony stimulating factor (G-CSF) alone to MM patients can produce sufficient CD34+ yields in the majority of patients. However, some patients may require > 4 apheresis days to achieve those yields. In addition, some patients may fail to collect enough CD34+ cells for ASCT. Plerixafor was approved in 2008 to be used in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood. Plerixafor can increase the average daily CD34+ yields by 3-fold. However, since the majority of patients can collect with G-CSF alone, a plerixafor algorithm was developed in 2009 to judiciously administer plerixafor only to those patients at higher perceived risk for mobilization failure. Administration of plerixafor is based on a peripheral blood CD34+ count drawn after 3 days of G-CSF and subsequent CD34+ collection yields. Methods: G-CSF 10mcg/kg/day (given daily or divided into twice daily) was administered subcutaneously from day 1 to 4. On day 4, a peripheral absolute CD34+ cell count was drawn. If the absolute CD34+ cell count was ≥ 12 cells/mm3 then apheresis started on day 5. If the absolute CD34+ cell count on day 4 was < 12 cells/mm3 plerixafor 240mcg/kg was administered subcutaneously the evening prior to apheresis beginning on day 5. During apheresis, if the CD34+ yield was < 1.0×106 CD34+/kg or 50% less than the previous collection, plerixafor was initiated. The minimum collection yield for all patients was 4.0×106 CD34+/kg. The maximum number of apheresis days was 5. Previous therapy was also examined. Results: From October 2009 to May 2011, 68 multiple myeloma patients were mobilized with G-CSF +/− plerixafor. Ninety-three percent (63/68) of patients achieved the minimum collection yield of 4.0×106 CD34+/kg. Ninety-nine percent (67/68) of patients achieved a yield of at least 2.0×106 CD34+/kg. Forty-four percent (30/68) of the patients required at least 1 dose of plerixafor with the majority requiring it prior to the first apheresis (83%). The median days of apheresis was 2 (range 1–5). The overall average yield on the first apheresis day was 4.35×106 CD34+/kg (95% CI +/− 0.64). The overall average total yield was 8.71×106 CD34+/kg (95% CI +/− 0.93). Sixty percent (41/68) and 76% (52/68) of patients collected ≥ 6.0×106 CD34+/kg in ≤ 2 days and ≤ 4 days of apheresis, respectively. The average daily yield (ACD34) for G-CSF alone can be predicted by ACD34 = 0.0377+ 0.07456xCD34 (see figure). ACD34 after plerixafor + G-CSF can be predicted by the equation 3(0.0377 + 0.07456xCD34) = ACD34. Of the patients that received previous radiation therapy (9) or cyclophosphamide (2), plerixafor was utilized in 78% and 100%, respectively. Previous lenalidomide therapy was present in 50% of the patients and it did not correlate to any increase in plerixafor usage. Conclusion: Adding plerixafor to G-CSF based upon a day 4 CD34+ count and collection yields is an effective strategy to mobilize CD34+ cells. Ninety-three percent of the of the patients were able to collect a minimum of 4.0×106 CD34+/kg cells and 99% collected > 2.0×106 CD34+/kg, in a median of two collections. Limitations to the study include a small sample size and an arbitrarily determined threshold to administer plerixafor. Also, the length of lenalidomide could not be retrospectively determined. A cost-based analysis is currently being performed to help determine the best day 4 CD34 cutoff for future studies. Disclosures: No relevant conflicts of interest to declare.

Bortezomib Given in Sequence with Anthracycline and Thalidomide-Containing Regimens Does Not Adversely Affect Stem Cell Mobilization and Engraftment in Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 541-541
Author(s):  
Geoffrey L. Uy ◽  
Nicholas M. Fisher ◽  
Steven M. Devine ◽  
Hanna J. Khoury ◽  
Douglas R. Adkins ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
High Dose Melphalan

Abstract Bortezomib (VELCADE®) is a selective inhibitor of the 26S proteasome proven to be safe and effective in the treatment of relapsed or refractory multiple myeloma (MM). While high-dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT) remains the standard of care, there is considerable interest in incorporating bortezomib into the initial treatment of MM. However, the role of bortezomib in frontline therapy for MM will depend in part on its effects on subsequent stem cell mobilization and engraftment. We conducted a pilot study of bortezomib administered pretransplant followed by high-dose melphalan with AHSCT. Two cycles of bortezomib 1.3 mg/m2 were administered on days 1, 4, 8, and 11 of a 21-day treatment cycle. One week after the last dose of bortezomib, stem cell mobilization was initiated by administering filgrastim 10 mcg/kg/day subcutaneously on consecutive days until stem cell harvest was completed. Stem cell collection began on day 5 of filgrastim via large volume apheresis (20 L/day) performed daily until a minimum of 2.5 x 106 CD34+ cells/kg were collected. Patients were subsequently admitted to the hospital for high-dose melphalan 100 mg/m2/day x 2 days followed by reinfusion of peripheral blood stem cells 48 hours later. Sargramostim 250 mcg/m2/day subcutaneously was administered starting day +1 post-transplant and continued until the absolute neutrophil count (ANC) ≥ 1,500/mm3 for 2 consecutive days. To date, 23 of a planned 40 patients have been enrolled in this study with 19 patients having completed their initial therapy with bortezomib followed by AHSCT. Patient population consists of 16 male and 7 female patients with the median age at diagnosis of 58 years (range 38–68). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (16), IgA (7) with stage II (9) or stage III (14) disease. Prior to receiving bortezomib, 11 patients were treated with VAD (vincristine, Adriamycin and dexamethasone) or DVd (Doxil, vincristine and dexamethasone), 5 patients with thalidomide and 5 patients with both. Two patients did not receive any prior chemotherapy. All patients successfully achieved the target of 2.5 x 106 CD34+ cells/kg in either one (15/19 patients) or two (4/19 patients) collections with the first apheresis product containing a mean of 5.79 x 106 CD34+ cells/kg. Analysis of peripheral blood by flow cytometry demonstrated no significant differences in lymphocyte subsets before and after treatment with bortezomib. Following AHSCT, all patients successfully engrafted with a median time to neutrophil engraftment (ANC ≥ 500/mm3) of 11 days (range 9–14 days). Platelet engraftment (time to platelet count ≥ 20,000/mm3 sustained for 7 days without transfusion) occurred at a median of 12 days (range 9–30 days). Eleven patients were evaluable for response at 100 days post-transplant. Compared to pre-bortezomib paraprotein levels, 3 patients achieved a CR or near CR, 7 maintained a PR while 1 patient developed PD. We conclude that pretransplant treatment with 2 cycles of bortezomib does not adversely affect stem cell yield or time to engraftment in patients with MM undergoing AHSCT. Updated results and detailed analysis will be available at the time of presentation.

Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2868-2868 ◽  
Author(s):  
Ingmar Bruns ◽  
Ulrich Steidl ◽  
Christof Scheid ◽  
Kai Hübel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cytotoxic Therapy ◽  
Cd 34 ◽  
Cd34 Cells

Abstract To date the most effective treatment for patients (pts) with multiple myeloma consists of conventional induction chemotherapy followed by either single or tandem high-dose chemotherapy and autologous blood stem cell transplantation. Collection of sufficient numbers of hematopoietic stem cells is essential for high-dose chemotherapy. Current regimens for stem cell mobilization are based on daily subcutaneous injections of human recombinant G-CSF starting shortly after cytotoxic therapy. Here we examined the use of polyethyenglycole (PEG)-conjugated G-CSF (pegfilgrastim) at two different doses in patients with stage II or III multiple myeloma. Patients received induction therapy with 2–4 cycles ID or VAD. Following cytotoxic therapy with cyclophosphamide (4g/m2) we administered either a single dose of 6 mg pegfilgrastim (n=10 pts; median age: 55 years), 12 mg pegfilgrastim (n=12 pts; median age: 51 years) or daily doses of 8,5 μg/kg unconjugated G-CSF (filgrastim) (n=12 pts; median age: 51 years). The growth factor was given on day 4 (range 2–5 days) in the “6 mg pegfilgrastim group”, on day 5 (range 2–7 days) in the “12 mg pegfilgrastim group” and on day 4 (range 3–6 days) in the “filgrastim group” after cyclophosphamide. Numbers of CD34+ cells were determined during leukocyte recovery and harvested by large volume apheresis using a cobe spectra blood cell separator. Pegfilgratim was associated with an earlier leukocyte recovery both at the 6mg dose (median 12 days, range 8–16 days) and the 12mg dose (median 12 days, range 7–16 days) as compared to filgrastim (median 14 days, range 11–15 days, p=0.04). Similarily, the peripheral blood CD34+ cell peak occurred earlier in patients who received pegfilgrastim (median 12 days, range 11–18 days versus median 15 days, range 12–18). On the other hand the peripheral blood CD 34+ peak did not differ significantly between the three groups (median 129/μl with 6 mg pegfilgrastim, range 30–433, median 78/μl with 12 mg pegfilgrastim, range 20– 1055 and median 111/μl with filgrastim, range 28–760, p=0.95). With a median of 1.0x10E7 CD34+ cells per kg (range 5.8x10E6-1.9x10E7) in the “6 mg pegfilgrastim group”, 7.4x10E6 CD34+ cells per kg (median, range 4.9x10E6- 3.8x10E7) in the “12 mg pegfilgrastim group” and 10.8x10E6 CD34+ cells per kg (median, range 5.0x10E6-8.7x10E7) in the “filgrastim group” there were no significant differences in the total number of harvested CD34+ cells. Following high-dose therapy with melphalan (200 mg/m2) and autografting leukocyte and platelet reconstitution was similar within all groups. In summary, a single dose of pegfilgrastim after high dose cyclophosphamide is capable of mobilizing a sufficient number of CD 34+ cells for succesful autografting and sustained hematological reconstitution in patients with multiple myeloma. No difference could be observed between 6 mg and 12 mg of pegfilgrastim. Our data provide the basis for randomized studies evaluating the optimal dose and timing of pegfilgrastim as well as long-term outcome in larger cohorts of patients.

Purified T Depleted Peripheral Blood and Bone Marrow Cd34 Transplantation from Haploidentical Mother to Child with Thalassemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3106-3106
Author(s):  
Pietro Sodani ◽  
Buket Erer ◽  
Javid Gaziev ◽  
Paola Polchi ◽  
Andrea Roveda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
Marrow Transplant ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract Approximately 60% of thalassemic patients can not apply to “gene therapy today” which the insertion of one allogenic HLA identical stem cell into the empty bone marrow as the vector of the normal gene for beta globin chain synthesis. We studied the use of the haploidentical mother as the donor of hematopoietic stem cells assuming that the immuno-tollerance established during the pregnancy will help to bypass the HLA disparity and allow the hemopoietic allogeneic reconstitution in the thalassemic recipient of the transplant. We have employed a new preparative regimen for the transplant in fourteen thalassemic children aged 3 to 12 years (median age 5 years) using T cell depleted peripheral blood stem cell (PBSCTs) plus bone marrow (BM) stem cells. All patients received hydroxyurea (OHU) 60 mg/kg and azathioprine 3 mg/kg from day -59 until day-11, fludarabine (FLU) 30 mg/m 2 from day -17 to day -11, busulphan (BU) 14 mg/kg starting on day -10, and cyclophosphamide(CY) 200mg/kg, Thiotepa 10 mg/kg and ATG Sangstat 2.5 mg/kg, followed by a CD34 + t cell depleted (CliniMacs system), granulocyte colony stimulating factor (G-csf) mobilized PBSC from their HLA haploidentical mother. The purity of CD34+ cells after MACS sorting was 98–99%, the average number of transplanted CD34+ cells was 15, 4 x 10 6/kg and the average number of infused T lymphocytes from BM was 1,8 x 10 5/Kg.The patients received cyclosporin after transplant for graft versus host disease(GVHD) prophylaxis during the first two months after the bone marrow transplantation. Results. Thirteen patients are alive. Four patients rejected the transplant and are alive with thalassemia One patients died six months after bone marrow transplant for central nervous system diffuse large B cell lymphoma EBV related. Nine patients are alive disease free with a median follow up of 30 months (range12–47). None of the seven patients showed AGVHD and CGVHD. This preliminary study suggest that the transplantation of megadose of haploidentical CD34+ cell from the mother is a realistic therapeutic option for those thalassemic patients without genotipically or phenotipically HLA identical donor.

Outcome of Patients with IgD and IgM Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplants: A Retrospective CIBMTR Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3328-3328
Author(s):  
Donna E. Reece ◽  
David H. Vesole ◽  
Smriti Shrestha ◽  
Angela Dispenzieri ◽  
Gustavo Milone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Small Sample Size ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Small Sample ◽  
Hematopoietic Stem ◽  
Prior Therapy

Abstract Multiple Myeloma (MM) is the most common indication for autologous hematopoietic stem cell transplantation (auto HCT). However, little information is available regarding the outcome of patients (pts) with the rarer immunoglobulin subtypes IgD and IgM, which represent 2% and 0.5%, respectively, of all MM cases. In addition, IgD MM has been reported previously to have a poorer prognosis, at least after conventional therapy. The CIBMTR conducted a retrospective analysis of MM pts transplanted between 1995–2005 to describe the characteristics and results of auto HCT in IgD (n=36) and IgM (n=11) among 3578 MM patients with auto HCT during this period. Median follow-up of survivors was 41 (range 2–130) months for pts with IgD and 58 (range 5–101) months for those with IgM MM. Among pts with IgD subtype, median age was 52 years (yrs), 67% were male, 36% had a creatinine >2 mg/L, 61% had Durie-Salmon stage III disease at diagnosis and 33% had Kappa Serum Light chain; the corresponding values for IgM pts were 58 yrs, 36%, 73% and 55% respectively. Prior to auto HCT, 75% of IgD pts were chemosensitive and 25% had received >2 lines of chemotherapy, while all IgM pts were chemosensitive and none had received more than 2 lines of prior therapy. Median time from diagnosis to auto HCT was 9 months in both subtypes. The most common conditioning regimen was singleagent melphalan, and all but 1 pt with IgD disease were grafted with blood stem cells. The small sample size precluded multivariate analysis for potential prognostic factors for outcome. Below table summarizes the post-auto HCT results in these pts contrasted with a reference pool of IgG and IgA MM receiving auto HCT in the same time period. Outcomes, probability (95% CI) IgD IgM IgG/IgA (n=36) (n=11) (n=1475) 100-day mortality, % 0 9 ( 0 – 32) 7 (5 – 8) Non MM deaths, % @ 1 yr 0 9 (0 – 32) 5 (4 – 7) @ 3 yrs 3 (0 – 13) 21 (2 – 51) 16 (14 – 18) Relapse/ Progression, % @ 1 yr 21 (9 – 37) 20 (2 – 49) 18 (16 – 20) @ 3 yrs 59 (41 – 76) 32 (8 – 64) 36 (34 – 39) Progression-free survival, % @ 1 yr 79 (63 – 91) 71 (41 – 93) 77 (74 – 79) @ 3 yrs 38 (21 – 56) 47 (17 – 78) 47 (44 – 50) Overall survival, % @ 1 yr 87 (74 – 97) 91 (68 – 100) 79 (77 – 85) @ 3 yrs 69 (51 – 84) 68 (36 – 93) 53 (50 – 57) No striking differences are apparent in the post auto HCT outcomes of patients with IgD and IgM MM. These results are also consistent with published outcomes of pts with IgD/ IgM MM (Wechaleker et al Ann Hematol. 2005 Feb; 84(2):115–7; Maisner et al Bone Marrow Transplant. 2008 Jan; 41(1):51–4).

Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 502-502 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Gerald Marit ◽  
Bernard Dazey ◽  
Jean-Michel Boiron ◽  
Zoran Ivanovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

Use of Plerixafor to Overcome Stem Cell Mobilization Failure: Long Term Follow up of Patients Proceeding to Transplant Using Plerixafor Mobilized Stem Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4390-4390 ◽  
Author(s):  
Abhinav Deol ◽  
Judith Abrams ◽  
Ashiq Masood ◽  
Zaid Al-Kadhimi ◽  
Muneer H. Abidi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Side Effects ◽  
Cell Count ◽  
Peripheral Blood ◽  
Cd 34 ◽  
Cd34 Cells ◽  
Significant Difference

Abstract Abstract 4390 Background: Plerixafor is a CXCR 4 antagonist which is now approved for use for stem cell (SC) mobilization with granulocyte colony stimulating factor (GCSF) in patients with non Hodgkin lymphoma (NHL) or multiple myeloma (MM). Prior to the approval of plerixafor, we enrolled 49 patients in a compassionate use protocol at our institution to mobilize SC for patients who previously failed at least one mobilization attempt. Methods: Patients received 0.24 mg/kg of plerixafor subcutaneously 9 –11 hrs prior to apheresis in addition to twice daily GCSF. Results: Median age of the patients was 64 years (range, 23–74 years). NHL was the most common diagnosis in 27 (55%) patients, followed by MM with 17(35%) patients and HD with 5 (10%) patients. Thirty nine patients (80%) had been treated with more than 2 chemotherapeutic regimens prior to the first attempt at stem cell collection. Thirty seven patients (76%) failed one previous mobilization attempt, while 12 (24%) had failed 2 or more previous attempts. Using the combination of Plerixafor and GCSF we collected ≥ 2.5 × 106 CD34+ cells/Kg in 33 patients (67%). The median days for pheresis were 1 day with a range of 1 to 3 days. The median SC dose collected was 4 × 106 CD34+ cells/Kg, with a range 2.5 – 14.3. The median CD-34+ peripheral blood count on the 1st day of their collection with plerixafor was 22.4/uL. In contrast the median peripheral blood CD-34+ cell count in these patients on the day of their first collection which failed was 6.2 /uL. The median increase using G-CSF and plerixafor was 14.9 CD-34+ cells/uL. We collected ≥ 2.5 × 106 CD34+ cells/Kg on 4/5 (80%) patients with HD, 13/17 (76%) patients with MM and 16/27 (59%) patients with NHL. Sixteen patients (33%) collected < 2.5 × 106 CD34+ cells/Kg. The median cell dose collected in these patients was 1.4 × 106 CD34+ cells/Kg with a range, 0.4–2.2. The median number of days of pheresis was 2 days (range, 1–4 days). In these16 patients the median CD-34+ count on the day of their previous failed collection was11.2/uL. Their CD-34+ cell count on their first day of collection after the use of G-CSF and plerixafor was 8.3/ul. Figure 1 shows the change in peripheral CD34 counts with the prior mobilization attempt and after plerixafor mobilization, for 38 patients in whom data was available. The most common side effects attributed to plerixafor were diarrhea, fatigue, thrombocytopenia and bone pain; observed in 12%, 8%, 8% and 6% patients, respectively. Forty three of the 49 patients proceeded to an autologus peripheral blood SC transplant, 34 patients received ≥ 2.5 × 106 CD34+ cells/Kg. Thirty two of these patients used the plerixafor collection as the only source of SC. Two patients had their plerixafor mobilized SC combined with a previous suboptimal SC collection. Nine patients received < 2.5 × 106 CD34 + cells/Kg; 4 patients received plerixafor mobilized SC alone, 5 patients received plerixafor mobilized SC combined with their previously mobilized SC. The preparative regimens used were R- BEAM (20 patients), Melphalan (16 patients), BEAM (6 patients) and Etoposide+TBI (1 patient). All patients received GCSF from day +6 till WBC engraftment. The median days of WBC and platelet engraftment were day +11 (range, 9–13 days) and day +16 (range, 11–77 days), respectively. There was no significant difference in days to engraftment between the patients who collected greater or less than 2.5 × 106 CD34 + cells/Kg. With a median follow up 13.7 months, long term engraftment data is available on 27 patients. The median white cell count, hemoglobin and platelet count 1 year after transplant was 4.7 × 109/L, 12.2 g/dL and 109 ×109/L, respectively. There was no significant difference in counts at the 1 year mark between patients who collected more or less than 2.5 × 106 CD34 + cells/Kg. To date 15 patients have evidence of disease progression. Two patients have developed MDS/AML post transplant. Conclusion: Overall, plerixafor leads to mobilization of sufficient stem cells in a vast majority of patients who have failed previous mobilization attempts and allows more patients to proceed to an autologous SC transplant. Plerixafor is well tolerated with minimal side effects, acceptable time to engraftment and acceptable peripheral blood counts at 1 yr after the transplant. Our analysis suggests that failure to increase peripheral CD34 count after plerixafor when compared to previous attempts may predict unsuccessful mobilization. Disclosures: Lum: Transtarget Inc: Equity Ownership, Founder of Transtarget.

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 ◽  
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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