Peripheral blood stem cell collection and transplantation using the Haemonetics Multi Component System

AIM: To assess clinical usefulness of an intermittent-flow blood cell separator in peripheral blood stem cell (PBSC) collection and transplantation. RESULTS: The Haemonetics Multi Component System (Multi) was used to collect PBSC (52 aphereses in 17 patients). The mean processing blood volume and the mean PBSC yield were 7407 ml and 2.16 x 10(6) CD34+ cells/kg, respectively. When CD34+ cells exceeded 0.3% of the peripheral WBC, more than 2.0 x 10(6) CD34+ cells/kg could be collected by a single apheresis. Eight patients underwent PBSC transplantation after high-dose chemotherapy. Hematopoietic recovery was achieved in a median period of 10 days. CONCLUSIONS: (1) A single-arm, light-weight machine has sufficient capability to collect PBSC. (2) The percentage of CD34+ cells in the peripheral WBC is a good predictor of the CD34+ cell yield of the collection.     

The number of CD34(+) cells in peripheral blood as a predictor of the CD34(+) yield in patients going to autologous stem cell transplantation

The number of CD34(+) cells in peripheral blood (PB) is a guide to the optimal timing to harvest peripheral blood progenitor cells (PBPC). The objective was to determine the number of CD34(+) cells in PB that allows achieving a final apheresis product containing > or =1.5 x 10(6) CD34(+) cells/kg, performing up to three aphereses. Between March 1999 and August 2003, patients with hematological and solid malignancies who underwent leukapheresis for autologous bone marrow transplantation were prospectively evaluated. Seventy-two aphereses in 48 patients were performed (mean 1.45 per patient; range 1-3). PBPC were mobilized with cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (G-CSF) (n = 40), other chemotherapy drugs plus G-CSF (n = 7), or G-CSF alone (n = 1). We found a strong correlation between the CD34(+) cells count in peripheral blood and the CD34(+) cells yielded (r = 0.903; P < 0.0001). Using receiver-operating characteristic (ROC) curves, the minimum number of CD34(+) cells in PB to obtain > or =1.5 x 10(6)/kg in the first apheresis was 16.48 cells/microL (sensitivity 100%; specificity 95%). The best cut-off point necessary to obtain the same target in the final harvest was 15.48 cells/microL, performing up to three aphereses (sensitivity 89%; specificity 100%). In our experience, > or =15 CD34(+) cells/microL is the best predictor to begin the apheresis procedure. Based on this threshold level, it is possible to achieve at least 1.5 x 10(6)/kg CD34(+) cells in the graft with < or =3 collections.     

Optimization of CD34+ collection for autologous transplantation using the evolution of peripheral blood cell counts after mobilization with chemotherapy and G-CSF.

BACKGROUND: Peripheral blood progenitor cells (PBPC) collection after high dose chemotherapy can be influenced by several factors. We searched for parameters that may predict the best day to start harvesting of PBPC in order to collect most CD34+ cells with the least number of aphereses. METHODS: We studied patients who underwent mobilization chemotherapy for autologous transplantation. The influence of age, sex, diagnosis, number of previous chemotherapy cycles, peripheral blood (PB) counts at day of mobilization (D0), day of neutrophils <1.0 x 10(9) l(-1) and day of nadir and interval between both (delta) on harvesting was investigated. Multivariate linear correlation models were built to predict the best harvesting with principles of parsimony. In patients where sequential CD34+ cell count was performed, the theoretical day of peak was calculated by interpolation in polynomial regression. RESULTS: One hundred and thirty four patients entered the analysis: 36 Hodgkin's lymphoma (HL), 65 B-large cell lymphoma (NHL) and 33 multiple myeloma (MM). Day of harvesting correlated with nr CHT, hemoglobin on D0, day of granulocytes <1.0 x 10(9) l(-1), delta and dosis of mobilization therapy. The day of CD34+ peak could be calculated by the formula = (-0.41) x Hemoglobin D0 + (day peripheral CD34+ cells = 10 x 10(6) microl(-1)) x 0.99 + 7.8. This model could explain 81% of the variance of the peak day and was stable by bootstrap resampling. Day of peripheral CD34+ cells = 10 x 10(6) microl(-1) preceded the calculated peak by 3-9 days. CONCLUSIONS: Although the day of best collection can be predicted using only sequential PB counts after mobilization chemotherapy, a model of prediction using peripheral CD34+ cell count is important especially for optimizing collection in poor mobilizing patients.     

Kinetics of PBPC mobilization by cyclophosphamide, as compared with that by epirubicin/paclitaxel followed by G-CSF support: implications for optimal timing of PBPC harvest

BACKGROUND: Limited information is available on the mobilization kinetics of autologous PBPCs after induction with various chemotherapy regimens. With PBPC mobilization in patients with breast cancer used as a model for chemotherapy-induced PBPC recruitment, the kinetics of progenitor cells mobilized either with cyclophosphamide (CY) or epirubicin/paclitaxel (EPI-TAX) followed by the administration of G-CSF was compared. STUDY DESIGN AND METHODS: The study included a total of 86 patients with breast cancer (stage II-IV) receiving either CY (n = 39) or EPI-TAX (n = 47), both followed by G-CSF support. The progenitor cell content in peripheral blood and apheresis components was monitored by flow cytometric enumeration of CD34+ cells. PBPC collection was started when the threshold of >20 x 10(6) CD34+ cells per L of peripheral blood was reached. RESULTS: The PBPC collection was begun a median of 9 days after the administration of EPI-TAX followed by G-CSF support, as compared to a median of 13 days after mobilization with CY plus G-CSF. After treatment with CY, the total numbers of PBPCs peaked on Day 1 of apheresis, and they rapidly declined thereafter. In contrast, treatment with EPI-TAX followed by G-CSF administration led to a steady mobilization of CD34+ cells during leukapheresis. The difference in the mobilization patterns with CY and EPI-TAX resulted in a greater yield of CD34+ cells per L of processed blood volume. Compared to EPI-TAX, mobilization with CY required the overall processing of 30 percent less whole-blood volume to reach the target yield of > or = 10 x 10(6) CD34+ cells per kg of body weight. After a median of three apheresis procedures, however, both CY+G-CSF and EPI-TAX+G-CSF were equally effective in obtaining this target yield. CONCLUSION: These results imply that specific PBPC mobilization as part of a given chemotherapy regimen should be taken into consideration before the planning of a PBPC harvest.     

The predictive value of white cell or CD34+ cell count in the peripheral blood for timing apheresis and maximizing yield

BACKGROUND: The collection of peripheral blood stem and progenitor cells (PBPCs) for transplantation can be time-consuming and expensive. Thus, the utility of counting CD34+ cells and white cells (WBCs) in the peripheral blood was evaluated as a predictor of CD34+ cell yield in the apheresis component. STUDY DESIGN AND METHODS: The WBC and CD34+ cell counts in the peripheral blood and the apheresis components from 216 collections were assessed. Sixty-three patients underwent mobilization with chemotherapy plus filgrastim, and 17 patients and 14 allogeneic PBPC donors did so with filgrastim alone. The relationship between the number of WBC and CD34+ cells in the peripheral blood and in the apheresis component was analyzed by using rank correlation and linear regression analysis. RESULTS: The correlation coefficient for CD34+ cells per liter of peripheral blood with CD34+ cell yield (x 10(6)/kg) was 0.87 (n = 216 collections). This correlation existed for many patient and collection variables. However, patients with acute myeloid leukemia had fewer CD34+ cells in the apheresis component at any level of peripheral blood CD34+ cell count. Components collected from patients with CD34+ cell counts below 10 x 10(6) per L in the peripheral blood contained a median of 0.75 x 10(6) CD34+ cells per kg. When the WBC count in the blood was below 5.0 x 10(9) per L, the median number of CD34+ cells in the peripheral blood was 5.6 x 10(6) per L (range, 1.0-15.5 x 10(6)/L). A very poor correlation was found between the WBC count in the blood and the CD34+ cell yield (p = 0.12, n = 158 collections). CONCLUSION: The number of CD34+ cells, but not WBCs, in the peripheral blood can be used as a predictor for timing of apheresis and estimating PBPC yield. This is a robust relationship not affected by a variety of patient and collection factors except the diagnosis of acute myeloid leukemia. Patients who undergo mobilization with chemotherapy and filgrastim also should undergo monitoring of peripheral blood CD34+ cell counts, beginning when the WBC count in the blood exceeds 1.0 to 5.0 x 10(9) per L.     

A single dose of 6 or 12 mg of pegfilgrastim for peripheral blood progenitor cell mobilization results in similar yields of CD34+ progenitors in patients with multiple myeloma

BACKGROUND: Current regimens for peripheral blood progenitor cell (PBPC) mobilization in patients with multiple myeloma are based on daily subcutaneous injections of granulocyte-colony-stimulating factor (G-CSF) starting shortly after cytotoxic therapy. Recently a polyethylene glycol-conjugated G-CSF (pegfilgrastim) was introduced that has a substantially longer t(1/2) than the original formula. STUDY DESIGN AND METHODS: The use of pegfilgrastim was examined at two dose levels for PBPC mobilization in patients with Stage II or III multiple myeloma. Four days after cytotoxic therapy with cyclophosphamide (4 g/m(2)), a single dose of either 6 mg pegfilgrastim (n = 15) or 12 mg pegfilgrastim (n = 15) or daily doses of 8 microg per kg unconjugated G-CSF (n = 15) were administered. The number of circulating CD34+ cells was determined during white blood cell (WBC) recovery, and PBPC harvesting was performed by large-volume apheresis. RESULTS: Pegfilgrastim was equally potent at 6 and 12 mg with regard to mobilization and yield of CD34+ cells. No dose dependence was observed because CD34+ cell concentration peaks were 131 and 85 per microL, respectively, and CD34+ cell yield was 10.2 x 10(6) and 7.4 x 10(6) per kg of body weight, respectively. Pegfilgrastim in either dose was associated with a more rapid WBC recovery (p = 0.03) and an earlier performance of the first apheresis procedure (p < 0.05) in comparison to unconjugated G-CSF. No difference regarding CD34+ cell maximum and yield could be observed. CONCLUSION: A single dose of 6 mg pegfilgrastim is equally potent as 12 mg for mobilization and harvest of PBPCs in patients with multiple myeloma. Because no dose dependency was seen at these dose levels, this might be also true for even smaller doses.     

Sequential transplants using mobilized peripheral blood progenitor cells

Modest success has been achieved with the use of high-dose cytotoxic therapy and bone marrow transplantation in solid tumors. Patient outcome can potentially be improved with further intensification of the therapy. The rapid hematologic recovery achieved with mobilized peripheral blood progenitor cells (PBPC) may reduce the toxicity of transplantation enabling the use of sequential courses of myeloablative therapy. We report on 42 patients with solid tumors enrolled in a tandem transplant protocol involving the use of PBPC mobilized with cyclophosphamide (4 g/m²), etoposide (1 g/m²), and granulocyte-colony-stimulating factor (G-CSF: 10 μg/kg/day). This regimen significantly increased the number of circulating progenitor cells; only 1-2 aphereses were sufficient to collect 2.5 × 10⁸/kg mononuclear cells, our goal for each transplant course. The median number of circulating colony-forming units (CFU) and CD34+ cells obtained for each transplant course were 70.3 × 10⁴/kg and 11.7 × 10⁶/kg, respectively. There was a significant correlation between the numbers of CD34+ cells and CFU measured in the apheresis product (r = 0.49, P = .003). The first transplant regimen given to 38 patients consisted of thiotepa, carboplatin, and cyclophosphamide. The second transplant regimen given to 29 patients consisted of busulfan and etoposide. Hematologic recovery was comparable after each of the two transplant courses. The median time to neutrophil recovery over 0.5 × 10⁹/L and to platelet transfusion independence was 9 and 8 days, respectively. There was no difference in engraftment rates after transplant with PBPC only (n = 28 courses) compared to transplant with PBPC plus bone marrow (n = 39 courses). There was a significant correlation between hematologic recovery after transplant and the number of CD34+ cells present in the PBPC. In conclusion, 1) PBPC are significantly mobilized with this combination chemotherapy and G-CSF, 2) mobilized PBPC result in rapid engraftment after myeloablative therapy, 3) hematologic recovery rates are comparable after sequential PBPC transplants, 4) PBPC alone are sufficient for long-term engraftment, and 5) rapid engraftment after PBPC transplant enables the use of a second course of myeloablative therapy within a short interval of time.     

Hematologic recovery after autologous PBPC transplantation: importance of the number of postthaw CD34+ cells

BACKGROUND: The implementation of a quality-assurance program is a major requirement to ensure quality and safety of the final PBPC components intended for clinical use. It is not clear whether the quantification of CFU-GM and CD34+ cells should be done on fresh components and after cryopreservation, which better represents the actual composition of the graft. STUDY DESIGN AND METHODS: Correlation between prefreeze and postthaw MNCs, CD34+ cells, and CFU-GM collected from 126 patients undergoing BMT (n=43) or PBPC (n =83) transplantation were evaluated. The statistical incidence of prefreeze and postthaw parameters as well as patient characteristics and conditioning regimens on hematologic recovery were analyzed. RESULTS: By multivariate analysis, prefreeze and postthaw CD34+ cells were the only two variables significantly and independently correlated to hematologic recovery. Low prefreeze and postthaw CD34+ cell numbers associated to a low CD34+ yield characterize PBPC grafts from patients who have the slowest hematologic recovery. The postthaw PBPC CD34+ cell number can be estimated before conditioning regimen by thawing a small aliquot of the graft. CONCLUSION: In association to prefreeze CD34+ cell number and to CD34+ yield, postthaw CD34+ cell number may be useful in monitoring cell loss during processing and identifying patients at risk of slow PBPC engraftment.     

A prospective randomized trial of two popular mononuclear cell collection sets for autologous peripheral blood stem cell collection in multiple myeloma

BACKGROUND: The COBE Spectra AutoPBSC collection set (AUTO-kit; CaridianBCT) is a popular dual-stage collection set for peripheral blood progenitor (PBPC) collection. Although the AUTO-kit is purportedly equivalent to the white blood cell (WBC) collection set (WBC-kit) for PBPC collection, improved CD34 yields after switching from the AUTO-kit to the WBC-kit were anecdotally observed, particularly in patients with higher WBC counts. A prospective, randomized trial of the AUTO- and WBC-kits for PBPC collection in multiple myeloma (MM) patients was therefore designed.
STUDY DESIGN AND METHODS: Sixty-eight MM patients were prospectively randomly assigned to either the WBC-kit or the AUTO-kit for PBPC collection. Primary study variables included the number of leukapheresis procedures per transplant, CD34/kg yield per procedure, and cumulative CD34/kg yield per mobilization cycle. Results were compared relative to collection kit and mobilization regimen. Statistics and graphics were performed with commercial software.
RESULTS: CD34/kg yields were higher with the WBC-kit, with 94% of chemotherapy-mobilized MM patients collecting 6 million CD34/kg in a single mobilization (p = 0.06). The WBC-kit also had a faster CD34 collection rate relative to peripheral CD34 counts. The AUTO-kit was significantly sensitive to high WBC counts, with a 50% decrease in CD34 collection efficiency and CD34 collection rate. This effect was specific to MM and not observed in lymphoma patients. Granulocyte–colony-stimulating factor mobilization and the AUTO-kit were associated with an increased incidence and severity of infusion reactions.
CONCLUSIONS: The WBC-kit performed consistently better than the AUTO-kit for PBPC collection in chemotherapy-mobilized MM patients, with fewer procedures per mobilization, superior collection rates, and a decreased incidence of infusion reactions.     

Volume-dependent collection of peripheral blood progenitor cells during large-volume leukapheresis for patients with solid tumours and haematological malignancies

We investigated the efficacy of peripheral blood progenitor cell (PBPC) collection during large-volume leukapheresis (LVL) in patients with solid tumours and haematological malignancies (n = 18). The time- and volume-dependent harvest of leucocytes (WBC), mononuclear cells (MNC), CD34+ cells and colony-forming cells (CFU-GM) during LVL was analysed in six sequentially filled collection bags processing four times the patient's blood volumes. The amounts of leucocytes (WBC) and the purity of mononuclear cells (MNC%) did not show any significant changes during LVL. The percentage of CD34+ cells remained constant for the first three bags but consecutively decreased from initially 1.71% CD34+ cells in the beginning of LVL to finally 1.34% CD34+ cells (P = 0.02). The mean numbers of colony-forming cells (CFU-GM) decreased from 74 microL-1 to 59 microL-1 during LVL (P = 0.16). Furthermore, the comparison of volume-dependent PBPC collection for patients with high, medium and low total yields of CD34+ cells showed similar kinetics on different levels for the three groups. We concluded that - relative to the initial total amount of PBPC harvested - comparable numbers of progenitor cells can be collected during all stages of LVL with a slight decreasing trend processing four times the patient's blood volumes.     

Factors influencing mobilization and engraftment in patients with metastatic breast cancer undergoing PBSC transplantation.

Factors influencing mobilization and engraftment of PBSC were analyzed in 38 patients with metastatic breast cancer who were undergoing PBSC transplantation. None of these patients had had previous chemotherapy for metastatic disease. PBSC were mobilized with cyclophosphamide (CY) and G-CSF (n = 21) or CY and etoposide (CY-etoposide) and G-CSF (n = 17). All received cyclophosphamide 6000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) as preparative regimen. PBSC infusion was followed by G-CSF at 5 microg/kg in 30 patients or 10 microg/kg in 8 patients. A median number of 27 x 10(6) CD34+ cells/kg was obtained with a median of four aphereses. Previous chemotherapy, radiation therapy, marrow disease, time from previous chemotherapy to mobilization, and type of mobilization regimen did not have a statistically significant effect on collection efficiency (CE). CE was defined as the total number of CD34+ collected/number of collections. Engraftment was rapid, with patients reaching a neutrophil count of 0.5 x 10(9)/L a median of 9 days (range 7-23) and a platelet count of 20 x 10(9)/L a median of 12 days (range 8-28) after transplantation. Shorter times to platelet recovery were associated with a higher number of CD34+ cells infused (p = 0.012), CY mobilization (p = 0.033), and a lower number of prior chemotherapy cycles (p = 0.022). When the number of CD34+ cells was included in the proportional hazard model, no other variables were found to be significant predictors of platelet engraftment. Time to neutrophil recovery was negatively associated with the dose of G-CSF used after transplantation (p = 0.036) CD34 cell dose is an important predictor of engraftment kinetics. A posttransplant dose of G-CSF improves neutrophil recovery. For patients with metastatic breast cancer and no previous chemotherapy for metastatic disease, we have no evidence for a difference between CY and CY-Etoposide as the mobilization regimen.     

NK细胞对小鼠异基因骨髓移植造血及免疫重建的影响

目的　研究自然杀伤 (NK)细胞在小鼠异基因骨髓移植 (allo BMT)中对造血及免疫重建的影响。方法　以近交系小鼠C5 7BL/ 6 (H 2 b)为供鼠、BALB/c(H 2 d)为受鼠 ,在allo BMT同时输入供鼠外周T细胞和 (或 )NK细胞 ,计数受鼠移植后不同时间的白细胞数 ;用流式细胞仪检测骨髓CD34 细胞和外周淋巴细胞中CD3 和CD19 细胞及表达供鼠基因的H 2Kb 细胞百分率 ,比较不同移植组存活率、植入水平、造血及免疫重建等。结果　输入供鼠外周NK细胞移植组与不输入NK细胞组比较 ,存活率显著增高 (6 0d存活率为 70 %vs 0 % ) ;白细胞计数、CD19 细胞及骨髓CD34 细胞计数恢复快 ;H 2Kb 细胞表达水平高 (86 .6 8± 4 .4 5vs 4 .6 8± 0 .32 )。移植后第 2 8天 ( 2 8天 )输入NK细胞组CD3 细胞水平 [(33.6 9± 3.36 ) % ]低于未输入NK细胞组 [(5 0 .4 0± 5 .0 6 ) % ](P <0 .0 1) ,在 6 0天两组比较差异无显著性 (P >0 .0 5 )。结论　在小鼠allo BMT中 ,同种异基因反应性NK细胞可以提高造血干细胞的植入水平、促进造血及免疫重建、增高移植受鼠的生存率。     

A multiple regression analysis on factors influencing haematopoietic progenitor cell collection for autologous transplantation

Autologous hematopoietic stem cell (HSC) transplantation today is the standard treatment for a wide variety of haematological and oncological diseases. HSC are collected from peripheral blood by leukapheresis (HPC-A) following chemotherapy and/or growth factor-mediated mobilization. The ideal HPC-A collection allows to reach the CD34(+) target dose through a single, tailored leukapheresis. The aim of this paper was to find out which collection parameter might play a key role in obtaining a CD34 dose >4×10(6)/kg with a reduced number of leukapheresis. To address this issue, a multivariate logistic regression was carried out on several operational and laboratory parameters from 943 HPC-A collections performed in 600 hematological and oncological patients. We observed a CD34(+) cells collection efficiency (CE) >50% when patient's pre-apheresis total WBC count was lower than 12.5×10(6)/mL. At the same time, the likelihood of reaching the CD34(+) cells target dose/kg increased from 6 to 3 times when the pre-apheresis WBC count ×10(6)/mL t was below 4.3 (OR=6.1; 2.6-14.1) and between 4.3 and 7 (OR=2.8; 1.4-5.7) respectively when compared to a pre-apheresis WBC count >36×10(6)/mL.     

A new model for predicting the timing of leukapheresis on the basis of CD34+ cell and hematopoietic progenitor cell levels

We developed a model (depending on peripheral CD34(+) cell count and hematopoietic progenitor cell count) to determine the optimal timing of 3-day leukapheresis in patients pretreated with chemotherapy and G-CSF. Marrow potentials were identified on the basis of three patterns of leukapheretic yield. Pattern 1 predicted good marrow potential. The positive predictive value of a first-day leukapheretic yield of >1 x 10(6) CD34(+) cells/kg (mean 3-day yield = 8.18 x 10(6) CD34(+) cells/kg, n = 11) was 100%. Pattern 2 predicted poor marrow potential. The negative predictive value of a 3-day leukapheretic yield of >1 x 10(6) CD34(+) cells/kg (3-day yield = 0.26 x 10(6) CD34(+) cells/kg, n = 1) was 100%. Pattern 3 met neither of the above criteria (mean 3-day yield = 1.37 x 10(6) CD34(+) cells/kg, n = 19). The marrow potential was borderline and patients could be further divided into two subgroups according to peripheral CD34(+) cell counts when WBC reached >10,000/microl. The mean yield differed significantly between pattern 1 and 3 (P < 0.001). For patients with good marrow potential, leukapheresis should begin as soon as the WBC count is >5,000/microl. Patients with borderline marrow potential may benefit from delaying leukapheresis until the WBC level is >10,000/microl and leukapheresis extended more than 3 days.     

Tempo of hematologic recovery correlates with peripheral blood CD34+ cell level in patients undergoing stem cell mobilization

This study was undertaken to evaluate the relationship between the time to recovery of peripheral blood counts and CD34+ cells in the peripheral blood (PB) and apheresis collections of patients undergoing intensive chemotherapy followed by rhG-CSF. Twenty-three patients with a median age of 42 years (range 17–64) with malignancies underwent peripheral blood stem cell (PBSC) collection after cyclophosphamide (CY) 4 g/m² and etoposide (600 mg/m²) followed by rhG-CSF (10 μg/kg/day). The WBC, platelet counts, CD34+ cell counts per ml of PB, and CD34+ cells in apheresis products were followed in all patients. The relationship of the time to recovery of WBC >1,000/μl, >3,000/μl, >10,000/μl and platelets >20,000/μl and 50,000/μl was compared to the average daily CD34+ cells/ml in each patient using the Spearman Correlation test. The tempo of recovery of WBC and platelets were highly correlated with the average CD34+ cell count in blood. In order to derive some useful guidelines for the timing of apheresis, the patients were divided into two groups, early recover (ER) and late recover (LR) based on the median time (day 10) to reach WBC count greater than 1,000/μl. ER patients had an average daily PB CD34+ cell count of 9.04 × 10⁴/ml (range 0.44–17.5) and a median yield of CD34+ cells of 10.43 × 10⁶/kg (range 0.60–25.95) compared to LR patients, who had 1.87 × 10⁴/ml (range 0.32–5.44) in the PB (P = .001) and a yield 3.20 × 10⁶/kg CD34+ cells (range 0.037–9.39) (P = .001). Patients recovering their WBC to 1,000/ml within 10 days of completing this regimen may undergo PBSC collection and achieve minimum-target cell doses of >2.5 × 10⁶ CD34+ cells/kg—100% of the time. J. Clin. Apheresis 13:1–6, 1998. © 1998 Wiley-Liss, Inc.     

Predicting hematopoietic stem cell mobilization failure in patients with multiple myeloma: a simple method using day 1 CD34+ cell yield

Early and reliable prediction of the likelihood of achieving adequate stem cell collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) would improve collection efficiency, prevent unnecessary aphereses, and permit appropriate treatment alterations. No previous study has reported a threshold CD34+ cell collection quantity on Day 1 or 2 of leukapheresis that could predict successful stem cell collection. We performed a retrospective analysis of all MM patients undergoing first attempt of stem cell collection at our institution from 2001 through 2008. Recursive partitioning analysis was used to identify Day 1 or Day 1+2 CD34+ collection quantity that predicted failure to reach target ≥ 2 × 10(6) CD34+ cells/kg within five days of collection. Totally, 172 patients were included in the analysis. Patients underwent mobilization with G-CSF or G-CSF+ chemotherapy. 23 of 172 patients (13.4%) failed to collect sufficient (≥ 2 × 10(6) CD34+ cells/kg) CD34+ cells after five days of apheresis: 22 of 29 who collected ≤ 0.70 × 10(6) CD34+ cells/kg and 1 of 143 who collected > 0.70 × 10(6) CD34+ cells/kg (75.9% vs. 0.7%, P < 0.001) on Day 1. Collection failure occurred in 23 of 30 patients who collected ≤ 1.54 × 10(6) CD34+ cells/kg and 0 of 142 who collected >1.54 × 10(6) CD34+ cells/kg (76.7% vs. 0%, P < 0.001) on Days 1 + 2. Day 1 CD34+ cell collection quantity identifies patients unlikely to achieve adequate collection for ASCT. Patients who collect ≤ 0.70 × 10(6) CD34+ cells/kg on day 1 could be considered for treatment modifications to improve CD34+ collection, such as early administration of plerixafor or large volume apheresis.     

Transfusion-associated iron overload as a predictive factor for poor stem cell mobilization in patients with haematological malignancies

Transfusion-associated iron overload is often observed in patients with haematological malignancies. We analysed the effect of iron overload, indicated by high serum ferritin level, on the mobilization of CD34(+) peripheral blood stem cells (PBSCs). We evaluated the association between the serum ferritin level prior to PBSC collection and the number of CD34(+) cells collected through leukapheresis in 51 patients with various haematological malignancies. Patients with serum ferritin level over 1000 ng mL(-1) were defined as high-ferritin group. Comparing the good (> or =1 x 10(6) per kg CD34(+) cells) and poor (<1 x 10(6) per kg CD34(+) cells) mobilizing groups, there was no difference in disease status, previous chemotherapies and white blood cell count at the first day of apheresis. However, there was a significant difference in the median units of red blood cell transfused between the good and poor mobilizer (2 vs. 8 units; P = 0.012). Serum ferritin level was notably higher in the poor mobilizer (1670 +/- 1320 ng mL(-1)) compared with the good mobilizer (965 +/- 705 ng mL(-1), P = 0.035). The cumulative number of CD34(+) cells per kg collected during the whole procedure was significantly lower in the high-ferritin group (5.5 +/- 4.7 x 10(6) per kg vs. 13.1 +/- 9.1 x 10(6) per kg, P = 0.01). Multivariate analysis revealed that serum ferritin level remained as an independent predictive factor for poor PBSC mobilization. Our study indicated that transfusion-associated iron overload is a predictive factor for poor PBSC mobilization. Iron chelation therapy prior to apheresis may be required to collect sufficient numbers of PBSCs in the iron overload patients.     

Evaluation of an algorithm based on peripheral blood hematopoietic progenitor cell and CD34+ cell concentrations to optimize peripheral blood progenitor cell collection by apheresis

BACKGROUND: Quantification of peripheral blood (PB) CD34+ cells is commonly used to plan peripheral blood progenitor cell (PBPC) collection but is time-consuming. Sysmex has developed a hematology analyzer that can quickly identify a population of immature hematopoietic cells (HPCs) according to cell size, cell density, and differential lysis resistance, which may indicate the presence of PBPCs in PB. This prospective study has evaluated the potential of such method to predict the PBPC mobilization. STUDY DESIGN AND METHODS: A total of 141 patients underwent PBPC mobilization. PB HPCs and PB CD34+ cells were simultaneously quantified with a hematology analyzer (SE2100, Sysmex) and flow cytometry, respectively. The number of blood volumes processed was then based on PB CD34+ cell concentration. RESULTS: The optimal PB HPC level able to predict a minimal level of 10 x 10(6) PB CD34+ cells per L was 5 x 10(6) per L with positive and negative predictive values of 0.93 and 0.36 percent, respectively. For this cutoff point, sensitivity and specificity were 0.81 and 0.65, respectively. The median number of blood volumes processed according to the PB CD34+ cell count allowed us to perform only one apheresis procedure for a majority of patients. CONCLUSION: PB HPC quantification is very useful to quickly determine the initiation of PBPC apheresis especially for patients with higher concentrations. For patients exhibiting a lower HPC count (<5 x 10(6)/L), other parameters such as a CD34 test may be needed. Such a policy associated with a length of apheresis adapted to the richness in the PB CD34+ cells allows for optimizing the organization of centers with an improvement in patient comfort and economical savings.     

Platelet count is a sensitive predictor of autologous peripheral blood progenitor cell collection yield in previously treated plasma cell disease patients

BACKGROUND: It is often a clinical dilemma to determine when to collect autologous peripheral blood progenitor cells (PBPCs) in patients who received prior chemotherapy. It is also challenging to predict if the collected cells will be enough for one or two transplants. STUDY DESIGN AND METHODS: A total of 103 PBPC donors were followed to evaluate factors that predict poor autologous PBPC collection. The donors were categorized into three groups: plasma cell disorders (PCDs), lymphomas, and normal allogeneic donors. RESULTS: Our evaluation showed that platelet (PLT) count before growth factor administration significantly correlated with total CD34+ cell yield (Spearman r = 0.38, p < 0.001). Further analysis showed this correlation was only significant in plasma cell disease patients who received prior chemotherapy (Spearman r = 0.5, p = 0.008). Baseline PLT counts did not correlate with PBPC collection yield in untreated PCD, lymphoma, and normal allogeneic donors. In addition, daily PLT count during PBPC harvest correlated with CD34+ cell yield for that day (Spearman r = 0.41, p < 0.001). With a multiple linear regression model (adjusted R(2) = 0.31, AIC = 63.1), it has been determined that the baseline PLT count significantly correlates with total CD34+ cell yield in treated PCD patients. CONCLUSION: Baseline PLT count is a sensitive indicator of autologous PBPC mobilization in PCD patients who received prior chemotherapy. This finding may be considered before growth factor administration to determine the optimal period to mobilize treated PCD patients and to predict if enough cells can be collected for one or two transplants.     

Second mobilization and collection of peripheral blood progenitor cells in healthy donors is associated with lower CD34(+) cell yields

We have retrospectively evaluated the results of two cycles of mobilization and collection of peripheral blood progenitor cells (PBPC) from 46 healthy donors included in the Spanish National Donor Registry. Mobilization involved the administration of granulocyte colony-stimulating factor (G-CSF) at a median dose of 10 microg/kg per day, and apheresis was begun after the fourth dose of G-CSF in both cycles. The median interval between both mobilizations was 187 days (range, 7-1428 days). The incidence and types of side-effects were similar after both donations, with 25 and 26 donors developing some toxicity after the first and second donations, respectively. The median number of CD34(+) cells collected was higher after the first mobilization than after the second (5.15 versus 3.16 x 10(6)/kg, respectively; p = 0.05), and 29 donors yielded fewer CD34(+) cells after the second mobilization (p = 0.018). A lower proportion of donors yielded CD34(+) cell counts >4 x 10(6)/kg after the second cycle than after the first (52% versus 76%, respectively; p = 0.057). Our study shows that second rounds of PBPC collection from normal donors are well tolerated but are associated with a significantly reduced number of CD34(+) cells collected when the same mobilization scheme is used.