Given Granulocyte Colony-stimulating Factor Research Articles

Risk of Febrile Neutropenia Associated With Select Myelosuppressive Chemotherapy Regimens in a Large Community-Based Oncology Practice.

Background: NCCN has classified commonly used chemotherapy regimens into high (>20%), intermediate (10%-20%), or low (<10%) febrile neutropenia (FN) risk categories based primarily on clinical trial evidence. Many chemotherapy regimens, however, remain unclassified by NCCN or lack FN incidence data in real-world clinical practice. Patients and Methods: We evaluated incidence proportions of FN and grade 4 and 3/4 neutropenia during the first chemotherapy course among patients from Kaiser Permanente Southern California who received selected chemotherapy regimens without well-established FN risk. Patients given granulocyte colony-stimulating factor (G-CSF) prophylaxis were excluded. Sensitivity analyses were performed to account for FN misclassification and censoring. Results: From 2008 to 2013, 1,312 patients with breast cancer who received docetaxel and cyclophosphamide (TC; n=853) or docetaxel, carboplatin, and trastuzumab (TCH; n=459); 1,321 patients with colorectal cancer who received capecitabine and oxaliplatin (XELOX; n=401) or leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX6; n=920); 307 patients with non-Hodgkin's lymphoma who received bendamustine with or without rituximab; and 181 patients with multiple myeloma who received lenalidomide with or without dexamethasone were included. Crude FN risk was >20% for both breast cancer regimens (TC and TCH). Crude FN risks for XELOX, FOLFOX6, bendamustine, and lenalidomide were <10%; however, when potential FN misclassification and censoring were considered, FN risks were >10%. Conclusions: Our results support published literature highlighting the real-world, "high" FN risk of the TC and TCH regimens for breast cancer. There is strong suggestive evidence that FN risks for XELOX, FOLFOX6, bendamustine, and lenalidomide are >10%. Calculation of chemotherapy course-level FN incidence without controlling for differential censoring for patients who discontinued regimens early, or possible FN misclassification, might have resulted in bias toward an underestimation of the true FN risk. These findings help define FN risk of the selected regimens in the real-world setting and inform prophylactic G-CSF use.

The First Case of Primary Cardiac Lymphoma, Diffuse Large B-Cell Type, Successfully Treated with EPOCH-R

Introduction:Primary cardiac lymphomas are rare non-Hodgkin lymphomas and account for less than 1% of intrinsic cardiac tumors and extranodal Non-Hodgkin lymphomas. Patients can present with a variety of manifestations including heart failure, chest pain, dyspnea, arrhythmias, and tamponade. Presently, there are no formal established guidelines for treatment of primary cardiac lymphomas.Presentation:This is a case of a 72-year-old white man with past medical history significant for paroxysmal atrial fibrillation and known pulmonary, renal, and cutaneous sarcoidosis who presented with palpitations, dyspnea on exertion and lightheadedness for two-weeks. He was evaluated by his cardiologist who recommended an elective atrial fibrillation radiofrequency ablation (RFA). Prior to the planned procedure a transesophageal echocardiogram was performed which revealed a large tissue density within the pericardial space, adjacent to the free wall of the right ventricle and right atrium, and invading the myocardium with extension through the interatrial septum (Figure 1). The RFA was aborted and the patient was admitted for further evaluation of the new cardiac mass, initially suspected to be cardiac sarcoidosis.Subsequent work up included a cardiac MRI, which displayed a dense 7.5 cm by 3.5 cm mass involving the right ventricle and right atrium, wrapping around the great vessels. Right heart cardiac catheterization with endomyocardial biopsy was performed which revealed clusters of large atypical B lymphoid cells with the following immunophenotype: CD30+, CD79a+, Pax5+, Alk 1-, CD138-, CD 10-, Bcl 2-, Bcl 6-, CD45-, focally CD20+, Ki67: 80-90% (Figure 2). These findings were consistent with diffuse large B cell lymphoma (DLBCL). His PET-CT demonstrated absence of extracardiac lesions, confirming the diagnosis of primary cardiac lymphoma (PCL) (Figure 3).The patient began treatment with a EPOCH-R (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) modified chemotherapy based regimen which consisted of a pre-phase treatment with dexamethasone 12 mg once daily for four days, a cumulative dose of cyclophosphamide 600 mg/m2 over five days and etoposide 50 mg/m2 for three days. Doses of cyclophosphamide and etoposide were initiated at lower doses and titrated upward to reach the target dose. This strategy was invoked based upon prior experiences and studies that suggest that a modest pre-phase cytoreduction reduces the risk of cardiac perforation. Rituximab was given on day six. He was also given granulocyte colony stimulating factor (GCSF).Our patient was observed closely in the cardiac intensive care unit throughout the duration of chemotherapy due to the high risk of fatal arrhythmia, tamponade, perforation and heart failure. Interim restaging, confirmed complete remission of the intracardiac mass. His post chemotherapy TTE demonstrated a slight reduction in ejection fraction (Figure 1). He received a total of three cycles of EPOCH-R and remained hemodynamically stable within the hospital. No further chemotherapy was given due to a decline in the patient's performance status.Conclusion:This is the first documented case of primary cardiac diffuse large B cell lymphoma successfully treated with EPOCH-R consisting of a modest pre-phase cytoreduction with steroids, cyclophosphamide and etoposide. The high area under the curve of doxorubicin in this setting is far less cardiotoxic. This regimen reduces the risk of cardiac perforation in patients with relatively normal ejection fractions. [Display omitted] [Display omitted] [Display omitted] DisclosuresO'Connor:Mundipharma: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; TG Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Spectrum: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; TG Therapeutics: Research Funding.

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates

Cell selection is an important part of manufacturing cellular therapies. A new highly automated instrument, the CliniMACS Prodigy (Miltenyi Biotec), was evaluated for the selection of CD34+ cells from mobilized peripheral blood stem cell (PBSC) concentrates using monoclonal antibodies conjugated to paramagnetic particles. PBSCs were collected by apheresis from 36 healthy subjects given granulocyte-colony-stimulating factor (G-CSF) or G-CSF plus plerixafor. CD34+ cells from 11 PBSC concentrates were isolated with the automated CliniMACS Prodigy and 25 with the semiautomated CliniMACS Plus Instrument. The proportion of CD34+ cells in the selected products obtained with the two instruments was similar: 93.6 ± 2.6% for the automated and 95.7 ± 3.3% for the semiautomated instrument (p > 0.05). The recovery of CD34+ cells from PBSC concentrates was less for the automated than the semiautomated instrument (51.4 ± 8.2% vs. 65.1 ± 15.7%; p = 0.019). The selected products from both instruments contained few and similar quantities of platelets (PLTs) and red blood cells. The depletion of CD3+ cells was less with the automated instrument (4.34 ± 0.2 log depletion vs. 5.20 ± 0.35 log depletion; p < 1 × 10(-6) ). Removal of PLTs from PBSC concentrates by washing was associated with better CD34+ cell recovery. We explored the reasons for lower CD34+ cell recovery by the Prodigy and found that the nonselected cells for the Prodigy contained more PLTs than those for the CliniMACS Plus. CD34+ cells can be effectively selected from mobilized PBSC concentrates with the CliniMAC Prodigy, but the recovery of CD34+ cells and depletion of CD3+ cells was lower than with the semiautomated CliniMACS Plus Instrument.

The Spleen Contributes Stem Cells to Peripheral Blood Stem Cell Transplants

Treatment of malignancies with Peripheral Blood Stem Cell Transplants (PBSCTs) from donors given Granulocyte- Colony-Stimulating-Factor (G-CSF) has improved survival relative to bone marrow transplants. G-CSF mobilizes CD34+ hematopoietic stem cells from bone marrow into the blood. Enrichment of PBSCT by purification of CD34+ stem cells fails to produce superior clinical benefits. We hypothesize that the reason why CD34+-enriched PBSCTs are not more effective is because the enrichment and purification process leaves out G-CSF-mobilized stem cells from another source, the spleen, which holds a unique reservoir of Hox11+ stem cells. Quantitative mRNA analysis was used to determine whether G-CSF mobilizes Hox11+ stem cells and whether expression occurs in a cell population distinct from CD34+ cells. Samples of peripheral blood lymphocytes (PBLs) were obtained from ten normal untreated donors and 18 normal donors treated with G-CSF. G-CSF was found to mobilize both CD34+ stem cells (p=0.02) and even more dramatically mobilize Hox11+ splenic stem cells (p=0.000013) into the peripheral blood. The findings support the hypothesis that G-CSF mobilizes two distinct stem cell populations, one from the bone marrow and the other from the spleen. The inferior clinical performance of CD34+-enriched and purified PBSCTs compared to unenriched PBSCTs may be explained by the omission of Hox11+ stem cells. These findings suggest that PBSCTs without enrichment and purification of CD34+ may improve treatment of cancer and potentially other diseases in tissues derived from Hox11+ stem cells.

Anti-CD25 instead of ATG for the Conditioning of HLA-Mismtched Hematopoietic Stem Cell Transplantation.

Abstract 4315 PurposeTo analysis the effect of Anti-CD25 instead of ATG for the conditioning of HLA-mismatched hematopoietic stem cell transplantation (HSCT). Methods21 cases underwent HLA-mismatched HSCT in our hospital from Mar. 2006 to May 2009. Diagnosis included ANLL(n=9)(2 in CR,7 in Relapse)?ALL(n=2), AHL(n=2), CML(n=4), MDS (n=2) and SAA (n=1), HLA Typing : All patients receive transplants from HLA-mismatched related donors. Among whom, 1,2 and 3 antigen mismatched were 11,8 and 2 cases respectively. Conditioning regimen consisted of modified BU/CY (n=12), BU/CY (n=6), FLU/BU (n=2) and CY/ATG for SAA(n=1). In addition, ATG(Thymoglobuline, 5-7.5mg/Kg, iv, divided into three days, -8∼-6d) was given for 8 patients. Anti-CD25 was given for 13 patients, including Daclizumab (50mg/d, -1?,03?,+4?,+11d) for 7 patients and Basiliximab (20mg/d, -1?,02?,+2?,+7d) for 6 patients. GVHD prophylaxis consisted of CSA and short course of MTX. In addition, MMF was given in all patients at the dosage 1.0 g/d for one month. The donors were given granulocyte colony-stimulating factor (G-CSF) at a dosage of 5 μg/Kg.d subcutaneously for 5 days, bone marrow was collected on day 3, peripheral blood stem cells were collected at day 4 and 5. ResultsEngraftment was obtained in all 21 patients, the median time to WBC >0.5×109/L and BPC>20×109/L in ATG and Anti-CD25 group were 14, 13d and 13, 12d, respectively (p>0.05), I∼II aGVHD accurred in 3 cases(37.5%) in ATG group and 5 cases(23.1%) in Anti-CD25 group,III∼IV aGVHD was observed in 1 case (12.5%) in ATG group and 2 cases (15.3%) in Anti-CD25 group. cGVHD was evaluable in 14 patients who survived after day +100, Extensive cGVHD developed in 1 (20%) of 5 patients in ATG group, and in 4 (44%) of 9 patients in Anti-CD25 group. Daclizumab and Basiliximab were not cause any infusion-related toxicity. Up to now, 13 patients survived in complete remission follow up 3-59 months, 4 cases (50%) died (3 in TRM and 1 in relapse) in ATG group, 4 cases (30.7%) died (1 in TRM and 3 in relapse) in Anti-CD25 group. ConclusionThe replacement of ATG with Anti-CD25 seems to be more safety and effective for the conditioning of HLA –mismatched HSCT. Disclosures:No relevant conflicts of interest to declare.

Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs

AbstractDuchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene on the X-chromosome that result in skeletal and cardiac muscle damage and premature death. Studies in mice, including the mdx mouse model of DMD, have demonstrated that circulating bone marrow–derived cells can participate in skeletal muscle regeneration, but the potential clinical utility of treating human DMD by allogeneic marrow transplantation from a healthy donor remains unknown. To assess whether allogeneic hematopoietic cell transplantation (HCT) provides clinically relevant levels of donor muscle cell contribution in dogs with canine X-linked muscular dystrophy (c-xmd), 7 xmd dogs were given hematopoietic cell (HC) transplants from nonaffected littermates. Compared with the pretransplantation baseline, the number of dystrophin-positive fibers and the amount of wild-type dystrophin RNA did not increase after HCT, with observation periods ranging from 28 to 417 days. Similar results were obtained when the recipient dogs were given granulocyte colony-stimulating factor (G-CSF) after their initial transplantation to mobilize the cells. Despite successful allogeneic HCT and a permissive environment for donor muscle engraftment, there was no detectable contribution of bone marrow–derived cells to either skeletal muscle or muscle precursor cells assayed by clonal analyses at a level of sensitivity that should detect as little as 0.1% donor contribution.

Effect of circulating blasts at time of complete remission on subsequent relapse-free survival time in newly diagnosed AML

AbstractStandardized criteria for complete remission (CR) in acute myeloblastic leukemia (AML) require the absence of peripheral blood blasts (PBBs). However, MD Anderson (MDA) criteria for CR (CR-MDA), although including the other requirements for CR, have not included the PBB count. We exploit this difference to assess the effect of PBBs at the time of CR-MDA on relapse-free survival (RFS) time. Eighty percent of the 533 patients with newly diagnosed AML or refractory anemia with excess of blasts (RAEB) entering CR-MDA from 1995 to 2000 had no PBBs at time of CR-MDA. Ninety-three percent of the remaining patients, who thus had CR-MDA but not standard CR, had 1% to 5% PBBs at this time. Multivariate analyses, using both conventional and Bayesian approaches, indicated that PBBs had no effect on RFS. For all patients and for the subgroups given and not given granulocyte colony-stimulating factor (G-CSF), the 95% credible interval for the relative risk of failure in the PBB group was nearly centered at 1.0. Thus, our data do not support use of PBBs in defining CR in newly diagnosed AML.

Pitfalls in the diagnosis of childhood leukaemia.

Pitfalls in the diagnosis of childhood leukaemia.

Composition of peripheral blood progenitor cell components collected from healthy donors.

Peripheral blood progenitor cell (PBPC) components are being collected from healthy donors for allogeneic transplantation, but the quantity, quality, composition, and variability of PBPCs collected from healthy people given granulocyte-colony-stimulating factor (G-CSF) have not been evaluated. PBPC components were collected from 150 healthy people who were given G-CSF (5, 7.5, or 10 microg/kg/day) for 5 days. The components were evaluated for white cell (WBC), mononuclear cell, CD34+ cell, neutrophil, platelet, and red cell (RBC) composition. The quantities collected were: WBCs, 35.0 +/- 16.4 x 10(9) (range, 11.9-163.3 x 10(9)); mononuclear cells, 33.3 +/- 14.4 x 10(9) (range, 11.9-139.6 x 10(9)); CD34+ cells, 412 +/- 287 x 10(6) (range, 70-1658 x 10(6)); neutrophils, 1.71 +/- 3.59 x 10(9) (range, 0-27.6 x 10(9)); RBCs, 7.2 +/- 4.0 mL (range, 0-22.1 mL); and platelets, 480 +/- 110 x 10(9) (range, 250-920 x 10(9)). PBPC components collected from people given G-CSF at 7.5 or 10 microg per kg per day contained significantly more CD34+ cells (respectively, 428 +/- 300 x 10(6); range, 70-1658 x 10(6) and 452 +/- 294 x 10(6); range, 78-1380 x 10(6)) than those from people given G-CSF at 5 microg per kg per day (276 +/- 186 x 10(6); range, 91-767 x 10(6)) (p = 0.007 and p = 0.002). When 10 microg per kg per day of G-CSF was given, 50 percent of the components contained enough CD34+ cells for transplantation to a 75-kg recipient (375 x 10(6) CD34+ cells), but 10.6 percent of the components contained less than 150 x 10(6) CD34+ cells and thus would provide a transplantable dose only for a 30-kg patient. One PBPC component collected from a healthy donor given 7.5 or 10 microg per kg per day of G-CSF should contain 70 to 1660 x 10(6) CD34+ cells, with 0 to 22 mL of RBCs. Because of the great variability in the number of CD34+ cells collected, the quantity of CD34+ cells in each component should be measured after each procedure to ensure that sufficient quantities of cells are present for a successful transplant.

Granulocyte Colony-Stimulating Factor–Induced Comobilization of CD4−CD8− T Cells and Hematopoietic Progenitor Cells (CD34+) in the Blood of Normal Donors

AbstractThe feasibility of transplantation of HLA-matched hematopoietic progenitor cells from the blood of normal donors given granulocyte colony-stimulating factor (G-CSF ) has been reported recently. In the current study, the changes in T-cell subsets as well as CD34+ cells were determined in one blood volume leukapheresis products of six normal individuals given G-CSF. Examination of the T-cell subsets in the leukapheresis products showed three different patterns: one in which a discrete population of CD4−CD8−αβ T cells was found in addition to the typical CD4+ and CD8+ T cells in the unfractionated as well as in high- and low-density cells; a second in which the discrete population of CD4−CD8−αβ T cells was predominant only in the low-density fractions; and a third in which a discrete population of CD4−CD8− T cells was not observed. The median yield of CD4−CD8− T cells was about fourfold to fivefold higher than the calculated number present in one blood volume (5L) from normal individuals. The ratios of CD34+ cells to CD4+ and CD8+ T cells, and of CD4−CD8− T cells to CD4+ and CD8+ T cells, were highest in the low-density fractions. These fractions suppressed the mixed leukocyte, and may ameliorate graft-versus-host disease as compared with unfractionated cells.

The kinetics of G‐CSF mobilization of CD34+ cells in healthy people

When healthy people are given granulocyte colony stimulating factor (G-CSF) for 10 days the number of CD34+ cells in the peripheral blood begins to increase on the fourth day, reaches a maximum on the sixth day and then decreases. In this study, we further define the time and variability of peak mobilization of CD34+ cells. Twenty-two healthy people were given G-CSF (7.5 or 10 micrograms kg-1 day-1) subcutaneously each morning for 5 days and peripheral blood CD34+ cell counts were analysed immediately prior to the fourth (day 4) and fifth (day 5) G-CSF injection and 24 h after the fifth injection (Day 6). White blood cell (WBC) and neutrophil counts were greatest on day 6 [WBC = 43.8 +/- 13.9 x 10(9) L-1 (mean +/- 1 SD) and neutrophils = 36.6 +/- 12.8 x 10(9) L-1]. In contrast the CD34+ cell counts on day 6 (107 +/- 104 x 10(6) L-1) were less than on day 5 (128 +/- 136 x 10(6) L-1) (P = 0.048) but still greater than on day 4 (60.7 +/- 40.2 x 10(6) L-1) (P < 0.0001). The CD34+ cell counts of 10 donors were measured 2, 4 and 6 h after the fifth injection to determine if the counts increased further between days 5 and 6. The number of CD34+ cells in the blood on day 5 2 h after the fifth injection (193 +/- 277 x 10(6) L-1) was greater than the number prior to the injection (158 +/- 190 x 10(6) L-1), 4 h post-injection (139 +/- 158 x 10(6) L-1) and 6 h post-injection (170 +/- 236 x 10(6) L-1), but the differences were not significant (P = 0.29, 0.25 and 0.45). The number of CD34+ cells in the blood of 12 people were measured before and after the fourth G-CSF dose. Prior to the day 4 injection the CD34+ count was 61 +/- 40 x 10(6) L-1. At 2, 4 and 6 h the counts were 60 +/- 40, 61 +/- 29 and 64 +/- 30 x 10(6) L-1, respectively, and the differences were not significant (P = 0.99, P = 0.98, and P = 0.73). In conclusion, when healthy volunteers are given daily G-CSF injections, the number of mobilized CD34+ cells was the greatest on day 5, slightly less on day 6 and the least on day 4. If only one PBSC component is needed, PBSCs can be collected on day 5 after only 4 days of G-CSF. If PBSC components are collected on both days 5 and 6, the fifth dose can be given either before or after the collection of the first PBSC component.

Fungemia in patients with hematologic malignancies: therapeutic effects of concomitant administration of fluconazole and granulocyte-colony-stimulating factor.

Serum (beta 1-->3)-D-glucan was elevated in 34 of 126 patients (27%) with hematologic malignancy who were clinically suspected of having a deep-seated mycosis. Although 11 patients (8.8%) were thought to have fungemia, fungi were isolated from blood culture in only 4. These results suggest that measurement of serum beta-D-glucan is useful for early diagnosis. Therapy with fluconazole (FLCZ) was effective in 9 of 11 patients (81.8%) suspected of having fungemia. Fungemia responded in 5 of 7 patients who were given granulocyte-colony-stimulating factor (G-CSF) concomitantly with FLCZ. This result suggested that administration of G-CSF with FLCZ was useful therapy for fungemia, which may occur during granulocytopenia following chemotherapy with anticancer agents.

Kinetics of Committed and Primitive Blood Progenitor Mobilization After Chemotherapy and Growth Factor Treatment and Their Use in Autotransplants

Peripheral blood cells (PBCs) collected by leukapheresis after progenitor mobilization with chemotherapy and growth factors have been used successfully to replace marrow autografts in protocols requiring stem-cell support. Moreover, such transplants are often associated with more rapid recovery of blood cell counts than is routinely achieved with bone marrow. While conditions that mobilize colony-forming cells (CFCs) into the circulation are becoming increasingly well characterized, little information is available as to how these or other mobilizing treatments may influence the release of more primitive cells into the peripheral blood. To quantitate the peripheral blood content of such cells, we used the long-term culture-initiating cell (LTC-IC) assay, which detects a cell type that is able to produce progeny CFCs after a minimum of 5 weeks in cultures containing marrow fibroblasts. In this report, we present the findings on 21 patients who were transplanted over a 7-year period at our institution with PBCs alone. PBCs were collected in steady-state (n = 6) or during the recovery phase after high-dose cyclophosphamide (Cy; n = 15, nine with and six without additional growth factor administration). PBCs collected from another 11 patients given granulocyte colony-stimulating factor (G-CSF) were transplanted together with autologous marrow. Time-course studies of nine patients after Cy +/- granulocyte-macrophage CSF (GM-CSF) showed that CD34+ cells, CFCs, and LTC-ICs fell from normal to undetectable levels after Cy, and increased at the time of white blood cell (WBC) recovery: LTC-ICs to a mean of sixfold and CFCs to a mean of 26-fold higher than normal. The mean number of CD34+ cells, CFCs, and LTC-ICs present in the PBC harvest was twofold to 10-fold higher after mobilization than in steady-state collections; however, more than 2-log interpatient variability was observed. After PBC transplantation, the median time to a WBC count more than 10(9)/L was 12 days; polymorphonuclear leukocyte (PMN) count more than 0.5 x 10(9)/L, 15 days; and platelet count more than 20 x 10(9)/L, 17 days, although patients who received fewer than 1.5 x 10(5) CFCs/kg had a more than 50% chance of delayed count recovery (> 28 days). Patients who received Cy + GM-CSF-stimulated PBCs had more rapid and consistent platelet recoveries as compared with other groups receiving Cy mobilized or steady-state PBCs alone, and a rapid WBC recovery after Cy predicted a rapid WBC recovery after transplantation.(ABSTRACT TRUNCATED AT 400 WORDS)

Kinetics of committed and primitive blood progenitor mobilization after chemotherapy and growth factor treatment and their use in autotransplants

Peripheral blood cells (PBCs) collected by leukapheresis after progenitor mobilization with chemotherapy and growth factors have been used successfully to replace marrow autografts in protocols requiring stem-cell support. Moreover, such transplants are often associated with more rapid recovery of blood cell counts than is routinely achieved with bone marrow. While conditions that mobilize colony-forming cells (CFCs) into the circulation are becoming increasingly well characterized, little information is available as to how these or other mobilizing treatments may influence the release of more primitive cells into the peripheral blood. To quantitate the peripheral blood content of such cells, we used the long-term culture-initiating cell (LTC-IC) assay, which detects a cell type that is able to produce progeny CFCs after a minimum of 5 weeks in cultures containing marrow fibroblasts. In this report, we present the findings on 21 patients who were transplanted over a 7-year period at our institution with PBCs alone. PBCs were collected in steady-state (n = 6) or during the recovery phase after high-dose cyclophosphamide (Cy; n = 15, nine with and six without additional growth factor administration). PBCs collected from another 11 patients given granulocyte colony-stimulating factor (G-CSF) were transplanted together with autologous marrow. Time-course studies of nine patients after Cy +/- granulocyte-macrophage CSF (GM-CSF) showed that CD34+ cells, CFCs, and LTC-ICs fell from normal to undetectable levels after Cy, and increased at the time of white blood cell (WBC) recovery: LTC-ICs to a mean of sixfold and CFCs to a mean of 26-fold higher than normal. The mean number of CD34+ cells, CFCs, and LTC-ICs present in the PBC harvest was twofold to 10-fold higher after mobilization than in steady-state collections; however, more than 2-log interpatient variability was observed. After PBC transplantation, the median time to a WBC count more than 10(9)/L was 12 days; polymorphonuclear leukocyte (PMN) count more than 0.5 x 10(9)/L, 15 days; and platelet count more than 20 x 10(9)/L, 17 days, although patients who received fewer than 1.5 x 10(5) CFCs/kg had a more than 50% chance of delayed count recovery (&gt; 28 days). Patients who received Cy + GM-CSF-stimulated PBCs had more rapid and consistent platelet recoveries as compared with other groups receiving Cy mobilized or steady-state PBCs alone, and a rapid WBC recovery after Cy predicted a rapid WBC recovery after transplantation.