The Application of Two Different Blood Cell Separators to Harvest CD34+ Cells in Patients Suffering from Non Hodgkin's Lymphoma

PurposeInteractions between the chemokine receptor CXCR4 and its ligand stromal derived factor-1 regulate hematopoietic stem-cell trafficking. AMD3100 is a CXCR4 antagonist that induces rapid mobilization of CD34+ cells in healthy volunteers. We performed a phase I study assessing the safety and clinical effects of AMD3100 in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL).Patients and MethodsThirteen patients (MM, n = 7; NHL, n = 6) received AMD3100 at a dose of either 160 μg/kg (n = 6) or 240 μg/kg (n = 7). WBC and peripheral blood (PB) CD34+ cell counts were analyzed at 4 and 6 hours following injection.ResultsAMD3100 caused a rapid and statistically significant increase in the total WBC and PB CD34+ counts at both 4 and 6 hours following a single injection. The absolute CD34+ cell count increased from a baseline of 2.6 ± 0.7/μL (mean ± SE) to 15.6 ± 3.9/μL and 16.2 ± 4.3/μL at 4 hours (P = .002) and 6 hours after injection (P = .003), respectively. The absolute CD34+ cell counts observed at 4 and 6 hours following AMD3100 were higher in the 240 μg/kg group (19.3 ± 6.9/μL and 20.4 ± 7.6/μL, respectively) compared with the 160 μg/kg group (11.3 ± 2.7/μL and 11.3 ± 2.5/μL, respectively). The drug was well tolerated and only grade 1 toxicities were encountered.ConclusionAMD3100 appears to be a safe and effective agent for the rapid mobilization of CD34+ cells in patients who have received prior chemotherapy. Further studies in combination with granulocyte colony-stimuating factor in patients with lymphoid malignancies are warranted.

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AMD3100 Plus G-CSF Mobilizes the Majority of Non-Hodgkin’s Lymphoma (NHL), Multiple Myeloma (MM), and Hodgkin’s Disease (HD) Patients Who Failed Prior Mobilization with Other Regimens.

Blood ◽

10.1182/blood.v108.11.5218.5218 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5218-5218

Author(s):

Gary Calandra ◽

John McCarty ◽

Joseph McGuirk ◽

Bart Barlogie ◽

Sue-Anne Crocker ◽

...

Keyword(s):

Multiple Myeloma ◽

Hodgkin's Disease ◽

Hodgkin’S Lymphoma ◽

Hodgkin’S Disease ◽

Median Number ◽

Disease State ◽

Hodgkin's Lymphoma ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Cd34 Cells

Abstract Background: AMD3100, an inhibitor of SDF1 binding to CXCR4, synergizes with G-CSF to allow mobilization of sufficient CD34+ cells/kg for autologous transplantation in pts unable to collect adequate CD34+ cells with G-CSF alone. Therefore, a single patient use (SPU) protocol for AMD3100 was adopted for more than one patient entry per site and termed Compassionate Use Protocol (CUP). The only difference of standard of care was the addition of AMD3100 to a G-CSF mobilization on the evening prior to each day of apheresis. Pts who could not proceed to apheresis due to low peripheral blood counts or pts who did not collect a minimum of 2 × 10^6 CD34+ cell/kg were eligible. Methods: Overall, more than 280 patients with proven poor mobilization including 137 NHL, 73 MM, and 31 HD have been included in CUP. A data audit was performed to validate data from pts with either non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), or Hodgkin’s Disease (HD). Sites were selected based on most patients entered, >3 of all diseases entered at a site, and sites conducting an AMD3100 trial. Audit included all pts, regardless of success or failure of the outcome; all information was collected on CRFs. Success of outcome was collection of ≥ 2×10^6 CD34+ cells/kg during the CUP procedure. CUP apheresis was done on day 5 after G-CSF (10mg/kg SC QD) and AMD3100 (240mg/kg SC Q10 PM) starting day 4. Results: Charts and CRFs were available for review for 115 pts; 63 (55%) were NHL patients from 29 sites, 35 (30%) were MM from 23 sites and 17 (15%) were HD from 13 sites. Of these pts, 58% were male, the median age was 59 years (range 21–77), 88% were Caucasian, and patient weight ranged from 43–128 kg. Prior treatments included a median of two regimens of chemotherapy in each of the three groups. Safety was generally favorable with no drug-related SAE’s and with an AE profile similar to that seen in research trials. The rates of successful collection of ≥ 2×10^6 CD34+ cells/kg per disease state as well as prior mobilization regimen are summarized in table 1. The median number of mobilizations for the successful patients was 3 days for NHL and HD and 4 for MM. Eighty-eight of the patients underwent transplantation with any cells. For example, of the 47 NHL patients transplanted, 24 had CUP only cells and 23 had mixed cells. The median number of days to engraftment was 11 for PMN and 18 for platelets. Long term follow up is limited, but there do not appear to be graft failures. At least 12 of the pts have died. Conclusions: AMD3100 in a poor mobilizer population is generally safe and well tolerated and is very effective in mobilizing > 2×10^6 CD34+ cells/kg. Mobilization success rate by disease state: overall and prior mobilization regimen Overall Prior Cytokine Prior Chemotherapy NHL 60% 53% 68% HD 76% 78% 75% MM 71% 73% 71%

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Randomized Comparison of Mobilization Kinetics of Circulating CD34+ Cells Between Biweekly CHOP and Dose-Escalated CHOP with the Prophylactic Use of Lenograstim (Glycosylated rHuG-CSF) in Aggressive Non-Hodgkin's Lymphoma

Leukemia & Lymphoma ◽

10.3109/10428190009059271 ◽

2000 ◽

Vol 38 (5-6) ◽

pp. 521-532 ◽

Cited By ~ 6

Author(s):

Kuniaki Itoh ◽

Tomoko Ohtsu ◽

Yasutsuna Sasaki ◽

Michinori Ogura ◽

Yasuo Morishima ◽

...

Keyword(s):

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Cd34 Cells ◽

Prophylactic Use ◽

Kinetics Of

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Preparation and successful engraftment of purified CD34+ bone marrow progenitor cells in patients with non-Hodgkin's lymphoma

Blood ◽

10.1182/blood.v85.6.1647.bloodjournal8561647 ◽

1995 ◽

Vol 85 (6) ◽

pp. 1647-1654 ◽

Cited By ~ 75

Author(s):

NC Gorin ◽

M Lopez ◽

JP Laporte ◽

P Quittet ◽

S Lesage ◽

...

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

Hodgkin’S Lymphoma ◽

Buffy Coat ◽

Hodgkin's Lymphoma ◽

Cloning Efficiency ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Cd34 Cells ◽

Macrophage Colony

From September 1992 to January 1994, we evaluated the use of the CEPRATE SC stem cell concentrator (CellPro, Inc, Bothell, WA) to select CD34+ cells from the bone marrow (BM) of 25 patients with non-Hodgkin's lymphoma in complete remission. This system uses the biotinylated 12.8 IgM MoAb to select CD34+ cells. Cells are retained on an avidin column and detached by agitation. Fifteen patients have been transplanted with the CD34+ purified fraction. The CD34+ purified fraction of the 25 processed BMs contained a median of 0.54% of the original nucleated cells in a volume of 5 to 10 mL. The median concentration of CD34+ cells was 49% (range, 12% to 80%), and the median enrichment of CD34+ cells was 33-fold (range, 9- to 85-fold). This selected CD34+ fraction retained 60% (range, 15% to 95%) of late granulocyte-macrophage colony- forming units (CFU-GM), 55% (range, 12% to 99%) of early CFU-GM, and 31% (range, 2% to 100%) erythroid burst-forming units (BFU-E) corresponding to median enrichments of 22-fold (range, 1- to 71-fold), 19-fold (range, 2- to 58-fold), and 14-fold (range, 2- to 200-fold), respectively. There was a correlation between immune phenotypes and progenitor cells. In the initial buffy-coat fractions, the percentage of CD34+ cells was correlated to the cloning efficiency of both late CFU-GM (P < .05) and early CFU-GM (P < .001). In the final selected fraction, there was a correlation between the percentage of CD34+/CD33- and the cloning efficiency of early CFU-GM (P < .05) and between the percentage of CD34+/CD33+ and the cloning efficiency of late CFU-GM (P < .05). Lymphoma cells positive for t(14; 18) were found by polymerase chain reaction in 9 of 14 buffy coats tested before CD34+ cell purification. In 8 cases, the CD34(+)-selected fraction was found to be negative, and the CD34- fraction was found to be positive. After cryopreservation, the recoveries of progenitor cells in the CD34(+)- purified fraction were 79% for late CFU-GM, 71% for early CFU-GM, and 73% for BFU-E. The 15 patients transplanted with the concentrated CD34+ fraction received a median dose of 1 x 10(6) CD34+ cells/kg (range, 0.3 to 2.96) and 10.62 x 10(4) early CFU-GM/kg (range, 0.92 to 25.55). Median days to recovery to 0.5 x 10(9)/L neutrophils and 50 x 10(9)/L platelets were days 15 (range, 10 to 33) and 23 (range, 11 to 68), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

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