Short and Long Term Efficacy of Autologous Bone Marrow Cells To Support Intensive Chemotherapy in Patients Failing Peripheral Blood Stem Cell Mobilization.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2999-2999 ◽  
Author(s):  
Tara Seshadri ◽  
Khalil Al-Farsi ◽  
Julie Stakiw ◽  
Clement Ma ◽  
Ronnie Saragosa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Intensive Therapy ◽  
Significant Proportion ◽  
Rank Test ◽  
High Dose ◽  
Transfusion Requirements ◽  
Significant Difference ◽  
The Impact

Abstract Introduction: Most autologous hematopoietic cell transplants (AHCT) are performed using peripheral blood mobilized progenitor cells (PBSC). However a small but significant proportion of patients (pts) are unable to mobilize adequate numbers of PBSC. The use of G-CSF-stimulated bone marrow (BM) derived progenitor cells is one method to circumvent this problem and enable AHCT to be performed. However, the long and short-term ability to engraft and the impact of this method on overall and progression free survival (OS and PFS) have not been established. Methods: We reviewed 52 pts (17 AML, 24 NHL, 11 HL) who failed PBSC collection between Jan 1999-Dec 2006 (<2×5106 CD34+cells/kg) and underwent G-CSF stimulated BM harvest to permit high dose therapy (etoposide 60 mg/kg + melphalan 160–180 mg/m2, + TBI 500 or 1200 cGy for pts with AML). 23 pts were supported by harvested BM (44%) and 29 (56%) with a mixture (Mx) of BM and PBSC. Overall and PFS was compared to pts undergoing AHCT using chemotherapy-mobilized PBSCs (n=440) in the same time period (AML n=32, NHL n=273, HL=135) who had a similar median age, pre-transplant induction, salvage therapy and intensive therapy regimens. Kaplan-Meier curves and the Log-rank test were used to compare the OS and PFS between cases and controls. Due to skewed data, the non-parametric Wilcoxon Rank Test was used for simple comparisons of clinical factors. Results: Median age of the cohort at AHCT was 43 years (range 24–68, 67% females). Status prior to AHCT was CR 44%, PR 54%, and SD 2%. Number of chemotherapy regimens (median):AML: 3; NHL: 3; HL: 2. Median BM CFU-GM infused was 4.4×104/kg and median PBSC infused was 0.1×106/kg (n=29). Median follow up times for AML/NHL/HL was 20, 18 and 50 months respectively. Twenty-three pts died:18 from disease progression, 4 treatment-related (TRM) and one of second cancer. Median engraftment time for neutrophils (>0.5×109/L) was 14 days and platelets (>20×109/L) was 27 days and was significantly longer compared to pts who received PBSC alone (10 and 11 days, respectively, p<0.0001). Pts receiving Mx grafts had significantly faster engraftment vs those receiving BM alone (p<0.001). Transfusion requirements (median) during the ASCT admission were 4 units for RBC and 25 units for platelets. Median 12 month Hb, platelet and neutrophil counts were 116 g/L (70–149), 113×109/L (21–238) and 2.4×109/L (0.3–6.2). Two year OS of patients who received harvested BM versus PBSC alone was: 63%/71% (AML, p=0.51), 57%/70% (NHL, p=0.04) and 71%/94% (HL, p=0.04). There was no significant difference in PFS between BM recipients and controls. Non relapse mortality was 5/52 (9.6%) for pts receiving BM compared to 18/440 (4%) supported by PBSCs. Conclusion: Performing an AHCT with BM in patients failing PBSC collection is feasible. Although engraftment is significantly delayed it appears sustained at 12 months post AHCT. Overall survival is inferior compared with patients receiving PBSC alone. Reasons for inferior disease-specific outcomes for pts with lymphoma receiving BM need to be determined.

Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison.

1995 ◽  
Vol 13 (6) ◽  
pp. 1328-1335 ◽  
Author(s):  
J Beyer ◽  
N Schwella ◽  
J Zingsem ◽  
I Strohscheer ◽  
I Schwaner ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Germ Cell Tumors ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Transfusion Independence ◽  
Transfusion Requirements ◽  
Peripheral Blood Progenitor Cells

PURPOSE To compare autologous bone marrow (BM) with peripheral-blood progenitor cells (PBPC) as hematopoietic rescue after high-dose chemotherapy (HDCT). PATIENTS AND METHODS From January 1991 until April 1993, 47 consecutive patients with relapsed or refractory germ cell tumors were randomized to either BM harvest or collection of PBPC mobilized by chemotherapy plus granulocyte colony-stimulating factor (G-CSF). After additional conventional-dose salvage treatment, all patients received HDCT with carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 with either BM or PBPC rescue. RESULTS Forty-six patients were assessable for hematologic reconstitution, and one patient died on day +4 before engraftment. Rescue using PBPC resulted in a significantly shorter recovery time to neutrophil counts more than 500/microL (10.0 v 11.0 days, P < .01), neutrophil counts more than 1,000/microL (10.0 v 12.0 days, P = .001), and platelet counts more than 20,000/microL (10.0 v 17.0 days, P < .01), as well as in fewer days to transfusion independence from RBCs (8.0 v 12.0, P < .05) and platelets (9.0 v 12.0, P < .01) and fewer days of intravenous (IV) antibiotics (9.0 v 11.0, P < .05). However, no statistical differences in transfusion requirements or in other clinical outcome variables were observed. Overall survival and event-free survival also were not different in the two study arms. CONCLUSION We conclude that the use of PBPC mobilized by chemotherapy plus G-CSF results in sustained trilineage reconstitution after HDCT, which occurs more rapidly as compared with BM. The earlier hematologic reconstitution in patients with PBPC rescue significantly reduces the time to transfusion independence.

scholarly journals Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2031-2035 ◽  
Author(s):  
NJ Chao ◽  
JR Schriber ◽  
K Grimes ◽  
GD Long ◽  
RS Negrin ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Platelet Recovery ◽  
Peripheral Blood Progenitor Cells ◽  
Significant Difference ◽  
Stimulating Factor

Abstract Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to “mobilize” peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with “nonmobilized” PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with “nonmobilized” recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving “mobilized” PBPC.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3254-3254
Author(s):  
Francesco Mazziotta ◽  
Gabriele Buda ◽  
Nadia Cecconi ◽  
Giulia Cervetti ◽  
Lorenzo Iovino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood ◽  
High Dose ◽  
Roc Curve Analysis ◽  
Cd34 Cells ◽  
Significant Difference ◽  
The Impact

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate > 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

Association of PML Expression with Chemotherapy-Resistance In Multiple Myeloma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2959-2959
Author(s):  
Daisuke Ohgiya ◽  
Makoto Onizuka ◽  
Hiromichi Matsushita ◽  
Naoya Nakamura ◽  
Hiroshi Kawada ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Chemotherapy Resistance ◽  
Nuclear Body ◽  
Rank Test ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 2959 Background: Although several novel agents have improved the prognosis of patients with multiple myeloma (MM), it still remains an incurable disease because of the difficulty to eradicate MM cells by current therapeutic approaches. Recent studies have revealed that a subset of malignant cells, cancer stem cells, contribute to chemotherapy-resistance in cancer treatment. Promyelocytic leukemia gene product (PML), known as a tumor suppressor through a variety of cellular functions in a nuclear macromolecular structure called the PML nuclear body, has been reported to be responsible for the chemotherapy-resistance by regulating cell cycle in chronic myeloid leukemia. We therefore investigated the impact of PML expression on the cellular proliferation status of MM cells and patients' prognoses. Materials/Methods: Bone marrow clot sections from 48 patients with newly diagnosed MM from Jan 1998 to Dec 2009 before any therapy at diagnosis were obtained, and analyzed, according to appropriate procedure approved by IRB at the Tokai University School of Medicine (Kanagawa, Japan) with written informed consent. They were doubly-stained with a combination of anti-PML/anti-CD138 and anti-Ki67/anti-CD138. For evaluation of the relation between PML status and cellular proliferation, the positive rates of PML and Ki67 in CD138 positive cells were compared. For investigation of the impact of PML expression on the prognosis of MM, the patients were divided into 3 groups, according to the PML positive rates in the CD138 positive cells: negative/low (less than 25 percentile: 12 cases), intermediate (from 25 to 75 percentile: 24 cases) and high (more than 75 percentile: 12 cases). Their overall survivals were compared using log-rank test. Furthermore, the PML positive rates between before and after treatments were compared using paired t-test. Results: The median observation period of 48 cases was 915 days. The median age of the patients was 62.5 (38-76) at diagnosis. All the patients were underwent combination chemotherapies containing alkylating agents as initial therapies. Two and nine patients were underwent allogeneic and autologous stem cell transplantation during the clinical courses, respectively. The numbers of patients of international staging system (ISS) stage I, II and III were 17, 14 and 17 cases. The PML positive rates in each case ranged from 0% to 83.8%. They were not correlated with ISS stages (Spearman r = 0.083) and the Ki67 positive rates (Spearman r = -0.13). The PML positive rates in the negative/low, intermediate and the high groups were less than 22.1%, from 22.1 to 56.6% and more than 56.6%, respectively. No significant difference in overall survival was observed among the 3 groups (p>0.05). However, there were significant differences in two year survival rate when the 3 groups were compared (100%, 85.2% and 54.7%; p=0.015) (Fig. 1). In 13 patients whose bone marrow clot sections were sequentially collected, the PML positive rates after treatments were significantly higher than those at diagnosis (p=0.0042) (Fig. 2). Especially, PML positive rates in all the 3 patients from the negative/low group were progressively increased (0.3 to 82.6%, 14.1 to 100%, 19.0 to 37.5%), and 2 of them died due to disease progression. On the other hand, 2 patients whose PML positive rates decreased after treatment were alive more than 5 years without therapies. Conclusion: Our data indicated that the level of the PML expression at diagnosis was a possible prognostic factor for early course of the disease (2 years after diagnosis). Chemotherapies might induce PML expression in MM cells or select PML positive MM cells. These findings suggest that PML expression presumably reflect chemotherapy-resistance in MM cells. The molecular mechanism of the association is now under investigation. Disclosures: No relevant conflicts of interest to declare.

Quality of life (QL) of patients (pts) treated for muscle invasive bladder cancer (MIBC) with radiotherapy (RT) +/- chemotherapy (CT) in the BC2001 trial (CRUK/01/004): Analysis of impact of treatment at an individual level.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 292-292 ◽  
Author(s):  
Robert Anthony Huddart ◽  
Emma Hall ◽  
Miguel Miranda ◽  
Malcolm Crundwell ◽  
Peter Jenkins ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Significant Proportion ◽  
Disease Free Survival ◽  
Similar Proportion ◽  
High Dose ◽  
Exact Test ◽  
Change Scores ◽  
Individual Level ◽  
Significant Difference ◽  
The Impact

292 Background: BC2001 showed that adding 5FU+MMC CT (cRT) to RT significantly improved locoregional disease free survival [James 2012] & using reduced high dose volume RT (RHDVRT) rather than standard RT (stRT) did not reduce late side effects [Huddart 2013]. Here we report the impact of treatment on QL at the individual level. Methods: 458 (pts) were randomised to RT (178) vs. cRT (182) (CT comparison) &/or to stRT (108) vs. RHDVRT (111) (RT comparison). Pts completed Functional Assessment of Cancer Therapy-Bladder (FACT-BL) questionnaires at baseline (bl), end of treatment (EoT), 6, 12, 24, 36, 48 & 60 months (m). Mean changes from bl were compared between randomised groups. A minimal clinically relevant change from bl score was defined as 3 points in bladder cancer subscale (BLCS) & 7 points in total FACT-BL (TOTAL). The proportion of pts with an improvement, no difference & worsening at 12m were compared by Chi squared/Fishers exact test (1% significance). Results: Data were available for 331 (92%) & 204 (93%) pts at bl & 181 (50%) & 107 (49%) at 12m for the CT & RT comparison respectively. QL scores were significantly reduced at EoT but recovered to bl levels by 12m with no significant difference in TOTAL or BLCS mean change scores between randomised groups. By EoT ~60% pts reported worsening of QL. At 12m & beyond, whilst mean change scores were not different to bl, ~30-40% reported worsening of QL (-) with a similar proportion reporting an improvement (+) (Table 1). No statistically significant differences were found between randomised groups. Conclusions: Following (c)RT a significant proportion of pts have a decline in QL at EoT but after 12m overall QL is, on average, similar to bl. At an individual level approximately equal proportions of pts report an improvement in QL as report a worsening. There is no evidence of additional impairment in QL by the addition of CT to RT. Clinical trial information: ISRCTN6832433. [Table: see text]

scholarly journals Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2031-2035 ◽  
Author(s):  
NJ Chao ◽  
JR Schriber ◽  
K Grimes ◽  
GD Long ◽  
RS Negrin ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Platelet Recovery ◽  
Peripheral Blood Progenitor Cells ◽  
Significant Difference ◽  
Stimulating Factor

Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to “mobilize” peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with “nonmobilized” PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with “nonmobilized” recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving “mobilized” PBPC.

scholarly journals Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3257-3262 ◽  
Author(s):  
Y Bastion ◽  
P Brice ◽  
C Haioun ◽  
A Sonet ◽  
G Salles ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
Peripheral Blood ◽  
Poor Prognosis ◽  
Intensive Therapy ◽  
Bone Marrow Involvement ◽  
Autologous Bone Marrow Transplantation ◽  
Conditioning Regimen ◽  
High Dose ◽  
Patients With Poor Prognosis

Intensive therapy, mainly with purged autologous bone marrow transplantation (ABMT), has been proposed in recent years as consolidation treatment in young patients with follicular lymphoma. Reported experience with transplantation of peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and the therapeutic efficacy of intensive therapy followed by unpurged autologous PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular lymphoma. Twelve patients were in first partial remission (PR), 34 were in second partial or complete remission (CR), and 14 were in subsequent progression. At the time of the procedure, 39 patients (65%) had persistent bone marrow involvement, 49 patients (82%) were in PR, and 16 patients had presented with a histologic transformation (HT). PBPC were collected after chemotherapy followed by granulocyte (G) colony-stimulating factor (CSF) or granulocyte-macrophage (GM)-CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen), or cyclophosphamide with or without etoposide plus total body irradiation (46 patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L was 13 days. There were five treatment-related deaths, with four being associated with a delayed engraftment and all occurring in patients in third or subsequent progression. At a median follow-up of 21 months, 48 patients were still alive, 18 relapsed, and seven died of lymphomas progression. Estimated 2-year overall survival (OS) and failure-free survival (FFS) rates were 86% and 53%, respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome. Patients with HT tended to have a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate of engraftment failure, the poor FFS observed in heavily pretreated patients suggests that intensive therapy should be performed early in the course of the disease. Given the high percentage of patients intensified in PR with residual bone marrow involvement, our results are comparable with those achieved with ABMT published to date. Prospective trials are warranted to compare this strategy with standard therapy in patients with relapsing or PR follicular lymphoma.

Association of bone marrow plasma cell infiltration pre-auto transplant with adverse outcomes in multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8102-8102
Author(s):  
Qaiser Bashir ◽  
Simrit Parmar ◽  
Yvonne Dinh ◽  
Sofia Qureshi ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Standard Of Care ◽  
Adverse Outcomes ◽  
Rank Test ◽  
High Group ◽  
Significant Difference ◽  
Bone Marrow Plasma ◽  
The Impact

8102 Background: Auto-stem cell transplantation (SCT) has become the standard of care for eligible patients (pts) with multiple myeloma (MM). However, the impact of bone marrow (BM) plasma cell (PC) percentage before SCT is not yet known. Methods: Retrospective review of 1489 MM pts who underwent auto-SCT from 7/8/98 – 12/31/2010 with post-induction, pre-SCT BM biopsy information available. Pts were divided into 2 groups: <10% PC infiltration (“PC low”) and >10% PC infiltration (“PC high”). Progression-free (PFS) and overall (OS) survivals were estimated by the Kaplan-Meier method. Log-rank test was performed to test differences in survival. Results: 1489 pts were studied. 1174 pts had <10% involvement of BM by PCs and 315 had > 10% involvement. For pts in the PC low group, 32% had a CR, 20% had a VGPR, 31% had a PR, 13% had <PR and 3% had progressive disease (PD) after SCT. For pts in the PC high group, 11% had a CR, 14% had a VGPR, 48% had a PR, 21% had <PR and 5% had PD after SCT. Median PFS was significantly shorter for the PC high group vs the PC low group (24.8 vs 29.5 months, p=0.05), as was median OS (52.5 vs 79.4 months respectively, p<0.001). When only pts who had a PR to induction were examined, there was a significant difference in both PFS (24.4 vs 33.2 months, p=0.04) and OS (58.3 vs 81.2 months, p =0.002) for the PC high vs PC low groups, respectively. For the 1299 (87%) pts treated in the era of novel therapeutics (after 2000), the differences between the PC high and PC low groups were maintained for both PFS (24.4 vs 29.5 months respectively (p=0.029)) and OS (54.8 vs 88.4 months respectively, p<0.001). Chemo-mobilization before SCT did not improve PFS or OS but this was done in only 44 (14%) of PC high pts. Conclusions: PC BM infiltration before auto-SCT is associated with a worse outcome. This finding persists in pts with a PR before SCT. Thus BM disease burden may further stratify pts with a PR. Though additional therapy did not significantly change the outcome for pts with high PC burden, this was done only in a minority of pts. Additionally, differences between PC high and PC low groups are maintained despite new salvage agents over the last 10 years. Further prospective study is warranted to determine the true impact of BM PC infiltration.

Reinfusion and serial measurements of carboplatin-mobilized peripheral-blood progenitor cells in patients receiving multiple cycles of high-dose chemotherapy.

1994 ◽  
Vol 12 (5) ◽  
pp. 1012-1020 ◽  
Author(s):  
T C Shea ◽  
J R Mason ◽  
M Breslin ◽  
E Bissent ◽  
M Mullen ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inverse Correlation ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Gm Csf ◽  
Peripheral Blood Progenitor Cells ◽  
Multiple Cycles ◽  
The Impact

PURPOSE To examine the ability of carboplatin to mobilize peripheral-blood progenitor cells (PBPCs) and to examine the impact of infusing these cells on myelosuppression following multiple cycles of high-dose therapy. Fluctuations in circulating progenitor cell concentration following repeated cycles of this therapy were also measured. PATIENTS AND METHODS Eight patients received a total of 20 cycles of carboplatin 1,200 mg/m2 per course, granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 micrograms/kg/d, and PBPC reinfusion every 28 days. PBPC were collected following 1 week of GM-CSF and following the first and second cycles of chemotherapy. Hematologic toxicity was correlated with the number of progenitor cells reinfused per cycle. The concentration of PBPC per milliliter of blood was measured at study entry, following GM-CSF priming, and after each cycle of chemotherapy. RESULTS We observed a strong inverse correlation between the number of PBPCs (CD34 and colony-forming unit granulocyte-macrophage [CFU-GM]), but not mononuclear cells (MNCs) reinfused and the days with neutropenia less than 500/microL and platelets less than 20,000/microL. Compared with baseline levels, the circulating PBPC concentration increased up to 27-fold following the first course of chemotherapy, but decreased toward, and eventually below, baseline following the second and third cycles of carboplatin. CONCLUSION PBPC reinfusion directly correlated with a reduction in myelosuppression following high-dose carboplatin chemotherapy. While high-dose carboplatin plus GM-CSF leads to a substantially greater mobilization of PBPC than GM-CSF alone, this effect is lost after multiple treatment cycles. These results emphasize the importance of early procurement and value of PBPC reinfusion in conjunction with multiple cycles of dose-intensive chemotherapy.

scholarly journals Cycling Status of CD34+ Cells Mobilized Into Peripheral Blood of Healthy Donors by Recombinant Human Granulocyte Colony-Stimulating Factor

Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1189-1196 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Agostino Tafuri ◽  
Alessandra Fortuna ◽  
Maria Teresa Petrucci ◽  
Maria Rosaria Ricciardi ◽  
...  
Keyword(s):  
Steady State ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Significant Proportion ◽  
S Phase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Stimulating Factor

Abstract In this study, we assessed the functional and kinetic characteristics of highly purified hematopoietic CD34+ cells from the apheresis products of 16 normal donors undergoing glycosylated granulocyte colony-stimulating factor (G-CSF ) treatment for peripheral blood stem cells (PBSC) mobilization and transplantation in allogeneic recipients. Mobilized CD34+ cells were evaluated for their colony-forming capacity and trilineage proliferative response to selected recombinant human (rh) CSF in vitro and the content of very primitive long-term culture initiating cells (LTC-IC). In addition, the cycling status of circulating CD34+ cells, including committed clonogenic progenitor cells and the more immature LTC-IC, was determined by the cytosine arabinoside (Ara-C) suicide test and the acridine orange flow cytometric technique. By comparison, bone marrow (BM) CD34+ cells from the same individuals were studied under steady-state conditions and during G-CSF administration. Clonogenic assays in methylcellulose showed the same frequency of colony-forming unit cells (CFU-C) when PB-primed CD34+ cells and BM cells were stimulated with phytohemagglutinin–lymphocyte-conditioned medium (PHA-LCM). However, mobilized CD34+ cells were significantly more responsive than their steady-state BM counterparts to interleukin-3 (IL-3) and stem cell factor (SCF ) combined with G-CSF or IL-3 in presence of erythropoietin (Epo). In cultures added with SCF, IL-3, and Epo, we found a mean increase of 1.5- ± 1-fold (standard error of the mean [SEM]) of PB CFU–granulocyte-macrophage and erythroid progenitors (burst-forming units-erythroid) as compared with BM CD34+ cells (P < .05). Conversely, circulating and BM megakaryocyte precursors (CFU-megakaryocyte) showed the same clonogenic efficiency in response to IL-3, granulocyte-macrophage–CSF and IL-3, IL-6, and Epo. After 5 weeks of liquid culture supported by the engineered murine stromal cell line M2-10B4 to produce G-CSF and IL-3, we reported 48.2 ± 35 (SEM) and 62.5 ± 54 (SEM) LTC-IC per 104 CD34+ cells in PB and steady-state BM, respectively (P = not significant). The Ara-C suicide assay showed that 4% ± 5% (standard deviation [SD]) of committed precursors and 1% ± 3% (SEM) of LTC-IC in PB are in S-phase as compared with 25.5% ± 12% (SD) and 21% ± 8% (SEM) of baseline BM, respectively (P < .001). However, longer incubation with Ara-C (16 to 18 hours), in the presence of SCF, IL-3 and G-CSF, or IL-6, showed that more than 60% of LTC-IC are actually cycling, with no difference being found with BM cells. Furthermore, studies of cell-cycle distribution on PB and BM CD34+ cells confirmed the low number of circulating progenitor cells in S- and G2M-phase, whereas simultaneous DNA/RNA analysis showed that the majority of PB CD34+ cells are not quiescent (ie, in G0-phase), being in G1-phase with a significant difference with baseline and G-CSF–treated BM (80% ± 5% [SEM] v 61.9% ± 6% [SEM] and 48% ± 4% [SEM], respectively; P < .05). Moreover, G-CSF administration prevented apoptosis in a small but significant proportion of mobilized CD34+ cells. Thus, our results indicate that mobilized and BM CD34+ cells can be considered equivalent for the frequency of both committed and more immature hematopoietic progenitor cells, although they show different kinetic and functional profiles. In contrast with previous reports, we found that PB CD34+ cells, including very primitive LTC-IC, are cycling and ready to progress into S-phase under CSF stimulation. This finding should be taken into account for a better understanding of PBSC transplantation.

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