Allogeneic hematopoietic stem cell transplantation for metastatic breast cancer

The prognosis is poor and the options are limited for patients with metastatic breast cancer (MBC), especially for those patients who have previously received taxanes and anthracyclines; treatment strategies are primarily palliative. Murine models have demonstrated that allogeneic T cells are capable of eliciting graft-versus-tumor (GVT) effects against breast cancer, inhibiting growth of breast cancer cell lines in vivo, providing the rationale to pursue allogeneic adoptive cellular therapy as a strategy to treat MBC. However, the clinical application of allogeneic hematopoietic stem cell transplantation (alloHSCT) was limited by concerns over toxicity and unproven efficacy. The development of non-myeloablative (a.k.a. reduced-intensity) conditioning regimens, which have less treatment-related mortality but preserve the T-cell mediated GVT effects, led to increased investigation of alloHSCT in MBC. Early reports of non-myeloablative alloHSCT indicate that a clinical GVT effect against breast cancer does exist. The responses, observed in 20-40% of patients, appear to be associated with the development of complete donor lymphoid chimerism and may be delayed. In its current form, alloHSCT by itself is unlikely to result in complete eradication of MBC; however, it may serve as a therapeutic platform to complement and enhance the effects of existing cytotoxic therapies and immunotherapies (e.g. trastuzumab), as well as therapies under development (e.g. vaccines). Current data on alloHSCT for MBC should be interpreted cautiously and carefully used for the design of future studies to fully determine the clinical efficacy of this form of adoptive cellular therapy in MBC.     

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma

Autologous stem cell transplantation (ASCT) improves survival in patients with previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive, aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic stem cell transplantation have been related to early absolute lymphocyte count (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the relation between ALC recovery and clinical outcomes in MM and NHL was not previously described. This is a retrospective study of patients with MM and NHL who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold was determined at 500 cells/microL on day 15 after ASCT. The study identified 126 patients with MM and 104 patients with NHL. The median overall survival (OS) and progression-free survival (PFS) times for patients with MM were significantly longer in patients with an ALC of 500 cells/microL or more than patients with an ALC of fewer than 500 cells/microL (33 vs 12 months, P <.0001; 16 vs 8 months, P <.0003, respectively). For patients with NHL, the median OS and PFS times were significantly longer in patients with an ALC of 500 cells/microL or more versus those with fewer than 500 cells/microL (not reached vs 6 months, P <.0001; not reached vs 4 months, P <.0001, respectively). Multivariate analysis demonstrated day 15 ALC to be an independent prognostic indicator for OS and PFS rates for both groups of patients. In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)     

Syngeneic hematopoietic stem cell transplantation for women with metastatic breast cancer

Metastatic breast cancer has been a common indication for autologous hematopoietic stem cell transplantation (HSCT). Previous reports indicate 3-year survival and progression-free survival (PFS) rates after autotransplant to be about 30 and 15%, respectively. Most deaths are from recurrent disease. One potential cause for high relapse rates is graft contamination with tumor. We describe 14 women with metastatic breast cancer transplanted between 1991 and 1998 with hematopoietic cells from identical twins. Median age was 41 y (range 34-50). Most women (12 of 14) were treated with mastectomy, and all received anthracycline-based regimens in their pretransplant course; nine women also received a taxane, seven radiotherapy and three hormonal therapy. Four women were in complete remission (one CR, three CRU) at transplant, five were in partial remission, two had stable disease and two had progressive disease. Eight women have died, one of treatment-related causes and seven of progressive breast cancer. Three-year survival was 48% (21-71%) and 3-year PFS was 21% (5-45%). Although the number of patients is small, outcomes for women transplanted with syngeneic grafts are similar to those of women receiving autologous grafts. This suggests that residual cancer in the patient is the major contributor to relapse after transplantation for breast cancer.     

Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma

Autologous stem cell transplantation (ASCT) is an effective treatment strategy for mantle-cell lymphoma (MCL) demonstrating significantly prolonged progression-free survival (PFS) when compared to interferon-alpha maintenance therapy of patients in first remission. The study of absolute lymphocyte count at day 15 (ALC-15) after ASCT as a prognostic factor in non-Hodgkin lymphoma (NHL) included different lymphoma subtypes. The relationship of ALC-15 after ASCT in MCL has not been specifically addressed. We evaluated the impact of ALC-15 recovery on survival of MCL patients undergoing ASCT. We studied 42 consecutive MCL patients who underwent ASCT at the Mayo Clinic in Rochester from 1993 to 2005. ALC-15 threshold was set at 500 cells/microl. The median follow-up after ASCT was 25 months (range, 2-106 months). The median overall survival (OS) and PFS times were significantly better for the 24 patients who achieved an ALC-15 >or=500 cells/microl compared with 18 patients with ALC-15 <500 cells/microl (not reached vs 30 months, P<0.01 and not reached vs 16 months, P<0.0006, respectively). Multivariate analysis demonstrated ALC-15 to be an independent prognostic factor for OS and PFS. The ALC-15 >or=500 cells/microl is associated with a significantly improved clinical outcome following ASCT in MCL.     

Early lymphocyte recovery following autologous peripheral stem cell transplantation is associated with better survival in younger patients with lymphoproliferative disorders

Early absolute lymphocyte count (ALC) has become an important end point for engraftment in patients undergoing autologous peripheral stem cell transplantation (APSCT). In this retrospective study, we evaluate the prognostic significance of early recovery of ALC ( > or = 0.5 cells x 10(9)/l on or before day 15) following APSCT in predicting transplant outcome in 72 patients with lymphoproliferative disorders, including non-Hodgkin's lymphoma (n = 30), Hodgkin's lymphoma (n = 8) and multiple myeloma (n = 34). The median quantities of CD34+ stem cells and lymphocytes infused were 4.97 x 10(6)/kg (range 0.64-11.7) and 11.3 x 10(7)/kg (range 1.11-110) respectively. After a median follow-up of 18 months (range 2-68), 28 patients had experienced a relapse and 16 had died. Of the 72 patients, 27 (37%) demonstrated early recovery of ALC. Early recovery of ALC was strongly associated with long-term overall and disease-free survival in patients aged less than 50 years (P < 0.001). In both univariate and multivariate survival analyses, a shorter time from diagnosis to APSCT was associated with early recovery of ALC (P = 0.03). These findings indicate that early recovery of ALC may contribute to longer survival in younger patients with lymphoproliferative disorders. A shorter time from diagnosis to APSCT may favor recovery of ALC independent of the infused stem cell or lymphocyte doses.     

Use of the anti-idiotype antibody vaccine TriAb after autologous stem cell transplantation in patients with metastatic breast cancer

Between April 1997 and March 1998 we evaluated the immune response and outcome in 11 chemosensitive patients who were treated with the anti-idiotype antibody vaccine TriAb after recovery from intensive therapy and autologous stem cell transplant (ASCT). Triab was commenced after recovery from the acute effects of ASCT; a minimum interval of 1 month was required from completion of consolidation radiotherapy, if given. Nine patients (82%) manifest anti-anti-idiotype antibody (Ab3) responses post ASCT. The maximal Ab3 response was seen after a median of 10 doses (range 5-20), which corresponded to a median of 14 months (range 5-19) post ASCT. Evidence of a T cell proliferative response was seen in eight patients; the response was modest in most of these. At a median follow-up of 24 months (range 22-33) after ASCT, four patients are alive without evidence of disease progression. All four of these patients were in the subgroup with more vigorous immune responses. Subsequent efforts have been directed toward the achievement of higher levels of immune responses more rapidly post ASCT. Bone Marrow Transplantation (2000) 26, 729-735.     

Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma

To understand the prognostic value of lymphocyte recovery after autologous peripheral blood stem cell transplantation (APBSCT), we performed a retrospective study of 59 newly diagnosed multiple myeloma (MM) patients who underwent frontline APBSCT. Conditioning regimens were melphalan 100 mg/m(2) for 2 days. Following APBSCT, all patients showed complete or partial response. Median follow-up time was 29.57 months and median recovery of absolute lymphocyte count (ALC) > or =1000/mm(3) was 23 days. Univariate analysis revealed that significant predictors of overall survival (OS) included bone marrow (BM) plasma cells < or =40% at diagnosis (P=0.0243) and recovery of ALC > or =1000/mm(3) by day +23 (P=0.0156). Positive predictors for progression-free survival (PFS) were BM plasma cells < or =40% at diagnosis (P=0.0134) and recovery of ALC > or =1000/mm(3) by day +23 (P=0.0243). Absolute neutrophil count > or =1000/mm(3) on day +12 was marginally significant for OS and PFS (P=0.0821 and P=0.1153, respectively). Multivariate analysis showed that ALC > or =1000/mm(3) on day +23 independently predicted OS (P=0.031) and prolonged PFS (P=0.011), and that serum beta2-microglobulin was marginally significant for prolonged OS (P=0.066). In conclusion, ALC recovery was an independent predictor of both OS and PFS in MM.     

Allogeneic hematopoietic cell transplantation for metastatic breast cancer

We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3-64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.     

Idiopathic pneumonia syndrome after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for high-risk breast cancer

Our aim was to describe the incidence, clinical course, and risk factors for idiopathic pneumonia syndrome (IPS) after high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa followed by autologous stem cell transplantation for high-risk breast cancer. Charts for patients who underwent high-dose chemotherapy for high-risk breast cancer at a single center from 1992 to 2000 were retrospectively reviewed, and potential risk factors for development of IPS were sought with the log-rank test. Of 164 patients reviewed, 20 developed IPS at a median onset of 87 days after the transplant (range, 2-257 days). The actuarial incidence of IPS in the first 100 days after the transplant was 8%, and 95% of patients developed symptoms within the first 6 months after transplant. Patient age, smoking status, breast cancer stage at diagnosis, and pretransplant lung function did not predict development of IPS. Three patients died of progressive pulmonary failure and the IPS resolved in the other 17. We concluded that IPS is an important cause of morbidity and mortality in patients with high-risk breast cancer undergoing high-dose chemotherapy. Given the absence of predictive factors, any pulmonary symptoms appearing in the first year after the transplant should be evaluated carefully.     

Immunologic recovery after autologous blood stem cell transplantation in patients with AL-amyloidosis.

We prospectively studied absolute lymphocyte (ALC) and monocyte counts (AMC), lymphocyte subsets and proliferative in vitro responses to mitogen and antigen in 12 patients with AL-amyloidosis (AL) undergoing autologous blood stem cell transplantation (SCT) with high-dose i.v. melphalan. Myeloid and lymphoid recovery (>500 per microl) occurred in a median of 10 days post SCT. While there was a continuous decline in the number of CD4+ T cells at 3 months, ALC, AMC, B cells (CD19+), CD8+ T cells, and NK cells (CD16+/56+) returned to baseline. While T cell proliferative responses to phytohemagglutinin (PHA) remained depressed, B cell function measured by the proliferative response to staphylococcal antigen returned to baseline by 3 months. To supplement our findings, we retrospectively evaluated ALC, AMC and serum immunoglobulin levels in a separate group of patients treated with the same protocol at our institution. ALC and AMC recovery was similar to the pattern observed in the initial study group. Immunoglobulin levels remained within normal ranges at 3 and 12 months after SCT. Of 50 patients who were followed for a minimum of 1 year following SCT, seven (14%) developed shingles and one (2%) had PCP pneumonia. In conclusion, cellular immune function, reflected by absolute numbers of CD4+ T cells and PHA responsive T cell proliferation, is significantly suppressed at 3 months after SCT in patients with AL, and this post-transplant immunosuppression is associated with a low but clinically meaningful occurrence of opportunistic infections typical of T cell immunosuppression.     

Dendritic cell recovery after autologous stem cell transplantation

There is persistent immunosuppression not only in allogeneic but also in autologous stem cell transplantation because humoral and cellular immunity may take a year or more to return to normal, with increased risk of infectious complications. This immune defect may also involve antigen presentation, in particular dendritic cell (DC) function. We evaluated DC subset reconstitution in 58 patients who underwent bone marrow (BM) or peripheral blood (PB) autologous haematopoietic stem cell transplantation (HSCT). In all patients DC type 1 (DC1) and DC type 2 (DC2) were already significantly lower than in normal individuals before conditioning therapy (DC1/microl 3.1 +/- 1.0, DC2/microl 3.0 +/- 1.1). On day 0 and day +7 the mean DC1 and DC2 numbers were very low in both groups. Patients who received unmanipulated marrow or peripheral blood stem cells reached pre-conditioning levels of DC1 and DC2 cells on day +20. In patients receiving selected CD34 cells, DC increased slowly and pre-transplant counts were observed only on day +60. Nearly 'normal' levels of DC1 and DC2 could be observed in the first group from day +180, and were maintained thereafter; in CD34(+) selected patients DC1 and DC2 counts remained lower than normal. Our data emphasise that circulating antigen presenting cells (APC) recover quickly. It remains to be determined if DC frequency in PB reflects their tissue function. The relatively low incidence of infections in patients undergoing autologous transplantation, despite defective lymphocyte reconstitution, could be related to functionally efficient DC.     

Relationship between early lymphocyte recovery and prognosis after allogeneic hematopoietic stem cell transplantation for acute leukemia in remission

To assess the relationship between early lymphocyte recovery and outcomes after allogeneic hematopoietic stem cell transplantation (SCT) for acute leukemia in remission, 79 adult patients (AML: 48, ALL: 31) who received transplantation between January 2000 and November 2009 were retrospectively analyzed. The median lymphocyte count on day 30 after SCT (LC30) was 465/μl (range, 10～2640). On comparison of clinical outcomes between patients with low (LC30<400/μl) and high (LC30≥400/μl) counts, the 5-year overall survival (OS) was significantly better in high LC30 group than in low LC30 group (81.6 vs. 52.6%, p=0.014), but the cumulative relapse rate (RR) and non-relapse mortality (NRM) at 5 years did not differ between the two groups. On multivariate analysis, low LC 30 (HR, 2.44; 95% CI, 1.02～5.88; p=0.046) and grade II～IV acute graft-versus-host disease (HR, 2.41; 95% CI, 0.99～5.90, p=0.0053) were significantly associated with worse OS. However, LC30 was not a risk factor for RR or NRM. These findings suggest that LC30 may be one of the outcome predictors for patients receiving SCT.     

Prolonged responses after autologous stem cell transplantation in African-American patients with multiple myeloma

Multiple myeloma (MM) has a double incidence in African-American (AA) than in non-AA patients and previous studies have shown a higher mortality in the former patient population. Here, we retrospectively analyzed the results of autologous stem cell transplantation (ASCT) in 38 AA and 32 non-AA consecutive patients. The two groups were comparable at diagnosis for age, stage of the disease, cytogenetic abnormalities, beta(2) microglobulin and albumin blood levels, and plasma cell marrow infiltration. The rates of complete and partial response observed in AA and non-AA patients after induction chemotherapy (9 and 42 vs 13 and 33%) and at 2 months (31 and 25 vs 30 and 20%) following ASCT were similar. At 6 months after ASCT, a greater relapse rate was observed in non-AA patients (P=0.009). At a median follow-up of 26 months, AA patients had a greater event-free survival (P=0.02) than non-AA patients, whereas overall survival was comparable in the two groups. The initial finding that AA patients with MM, compared to non-AA patients, had more prolonged responses and comparable survival after ASCT suggests that intensified chemotherapy is equally effective in patients of various ethnicities.     

Severe mucositis is associated with reduced survival after autologous stem cell transplantation for lymphoid malignancies

Mucositis is a known complication of autologous stem cell transplantation (ASCT). This study retrospectively reviewed 191 patients with lymphoid malignancies undergoing ASCT following a uniform mobilising regimen of etoposide (VP-16)/granulocyte colony-stimulating factor and a uniform high-dose preparative regimen of busulfan/cyclophosphamide/VP-16. Eighty-seven patients experienced severe mucositis (modified Oral Mucositis Assessment Scale > or =1). Patient characteristics compared between mucositis groups were balanced according to disease status, prior exposure to radiation therapy, time from radiation therapy and actual body weight. Log-rank analysis revealed that severe mucositis was associated with inferior overall survival (P = 0.002). A 12-month landmark analysis showed this difference in survival occurred within 1 year post-transplant. Multivariate analysis of all-cause mortality showed lower pretransplant albumin and severe mucositis to be significant risk factors. Multivariate analysis for relapse mortality revealed severe mucositis to be a risk factor (P = 0.047), while lower pretransplant albumin was significant for non-relapse mortality (NRM; P = 0.009). Kaplan-Meier estimates of survival based on relapse and NRM were significantly worse for patients with severe mucositis. Reduced pretransplant forced expiratory volume in 1 s (FEV(1)) and carbon monoxide (CO) diffusing capacity (DLCO) were also associated with severe mucositis. Our data suggest that studies of new treatment strategies for mucositis should include relapse and survival endpoints and that pretransplant factors, such as FEV(1) and DLCO may be useful to risk-stratify patients entered onto such trials.     

Outpatient autologous hematopoietic stem cell transplantation for patients with relapsed follicular lymphoma

Autologous stem cell transplantation (ASCT) has emerged as a viable option for the treatment of relapsed follicular non-Hodgkin’s lymphoma. We report on the outpatient experience of 60 patients who underwent ASCT for this condition. The median age was 51 years (30–65). Pre-transplantation conditioning regimens consisted of either etoposide/melphalan/TBI, CBV or BEAM. Patients participated in this transplant program for a median of 20.5 days (14–78), and 58.4% of the total program days were spent in the outpatient setting. Six patients were well enough to be treated solely as outpatients. Ninety percent of patients required at least one inpatient admission (median 7 days), and 70% of first inpatient transfers occurred within the first week following transplant and always before day +12. There were no predictors for prolonged inpatient stays. Febrile neutropenia and gastrointestinal toxicity were the main reasons for inpatient transfers. No outpatient required an urgent admission to the ICU or died in the outpatient setting. The treatment-related mortality at days 30 and 100 was 0 and 1.7%, respectively. The overall and progression-free survivals at 5 years were 65.7 and 56.1%, respectively. Outpatient ASCT with total body irradiation is feasible, safe, and effective for patients with relapsed follicular lymphoma.     

High-dose chemotherapy with autologous stem cell transplantation in patients with oligometastatic breast cancer

The purpose of this prospective trial was to study a combined-modality treatment including local consolidation by surgery or radiotherapy and high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell (PBSC) transplantation. In all, 48 patients with oligometastatic breast cancer amenable to local treatment after induction chemotherapy with epirubicin and cyclophosphamide or paclitaxel and cisplatin, depending on prior adjuvant chemotherapy, were enrolled. The median follow-up was 41 months (range, 7-85 months). PBSC were collected in 47 patients, and 40 received one or two courses of HDC. Local therapy was given in 37 patients. No treatment-related deaths occurred. Of 47 evaluable patients, 36 (75% of intention-to-treat population) had no evidence of disease or complete remission after completion of therapy. Six patients (12.5%) had partial response, two patients (4%) no change, and three patients (6%) progressive disease. The median time to progression and overall survival was 17.5 (95% confidence interval (CI), 14-21 months) and 42.2 months (95% CI, 33-52 months), respectively, and 27% of patients were progression free after 5 years. In conclusion, patients with oligometastatic breast cancer can be treated safely with this combined modality protocol with promising relapse-free survivals.     

Factors influencing hematopoietic recovery after autologous blood stem cell transplantation in patients with acute myeloblastic leukemia and with non-myeloid malignancies

Factors influencing hematopoietic recovery (HR) after autologous blood stem cell transplantation (ABSCT) were analyzed in 73 patients with various non-myeloid malignancies (NMM), and in 58 patients with acute myeloblastic leukemia (AML). Peripheral blood stem cells were collected following mobilization with chemotherapy, granulocyte colony-stimulating factor (G-CSF), or chemotherapy plus G-CSF. The conditioning regimen used consisted of either chemotherapy alone (112 cases) or chemotherapy plus total body irradiation (19 cases). The median number of colony-forming units granulocyte-macrophage (CFU-GM) was similar in both groups of patients, with the median number of CD34(+) cells infused being higher in the AML group (5.4 vs 4 x 10(6)/kg; P = 0.03). Median time neutrophils >0.5 x 10(9)/l was 13 days in both groups, and median time to a platelet count >20 x 10(9)/l was longer in AML patients (14 vs 12 days; P = 0.01). In multivariate analysis, the only factors affecting neutrophil recovery in the NMM group were the CD34+ cell number (continuous model) and the CFU-GM dose (categorized model) infused, whereas for platelet recovery, previous chemotherapy also remained significant. In the AML group, the only factors significantly affecting the speed of neutrophil recovery were dose of CD34+ cells administered and the patient's age. As for platelet recovery, only the progenitor dose administered remained significant. In the NMM group, the most discriminating cut-off values for a rapid neutrophil and platelet recovery were 1.5 x 10(6) and 2.5 x 10(6) CD34+ cells/kg, respectively, and for AML patients these figures were 1.5 x 10(6) and 4 x 10(6) CD34+ cells/kg, respectively. Our results confirm the slower HR after ABSCT in AML, and highlight the importance of progenitor cell dose in accelerating HR after ABSCT.     

High CD8+ lymphocyte dose in the autograft predicts early absolute lymphocyte count recovery after peripheral hematopoietic stem cell transplantation

Early lymphocyte recovery (ELR) after autologous peripheral hematopoietic stem cell transplantation (ASCT) is an independent predictor for survival in patients with hematological and non‐hematological cancers. Sixty‐five ASCT for hematological cancers were retrospectively analyzed to identify the factors associated with ELR and to assess the impact of different mobilization regimens on the pre‐collection absolute lymphocyte count (ALC). The CD8+ lymphocyte dose in the autograft and the pre‐mobilization ALC were independently associated with ELR (P < 0.001 and P = 0.008, respectively). CD8+ lymphocyte doses higher than 0.1 × 10⁹/kg were strongly associated with ELR [P < 0.001, odds ratio 25.22, 95% confidence interval (CI) 4.98–127.69] and this cutoff may be used to predict ELR (P = 0.001, area under the curve 0.75, 95% CI 0.62–0.88). Mobilization with granulocyte colony‐stimulating factor (G‐CSF) alone, the pre‐collection ALC and the number of apheresis sessions were independently associated with the CD8+ lymphocyte dose (P = 0.04, P = 0.001, and P < 0.001, respectively). The number of aphereses was the variable with the strongest correlation to the CD8+ lymphocyte dose (r_s = 0.68, P < 0.001). Median pre‐mobilization ALC was higher than pre‐collection ALC in the subgroup of patients without ELR mobilized with chemotherapy followed by G‐CSF (1090 vs. 758 lymphocytes/μL; P < 0.001). This reduction was not significant in the subgroup with ELR mobilized with chemotherapy plus G‐CSF (1920 vs. 1539/μL, respectively; P = 0.23). These results suggest that the CD8+ lymphocyte dose in the autograft is critical for ELR after ASCT and also demonstrates that mobilization with chemotherapy followed by G‐CSF significantly decreases the pre‐collection ALC, especially in patients with low pre‐mobilization ALC. Am. J. Hematol, 2009. © 2008 Wiley‐Liss, Inc.