Short-term gonadotropin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation.
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Adult↗
Biomedical subjects
B Witt
Publications and source records attributed to B Witt.
Abnormal sperm morphology is highly predictive of pregnancy outcome during controlled ovarian hyperstimulation and intrauterine insemination.
PURPOSE: The purpose of this study was to assess the predictive value of a modified form of Kruger's strict criteria for sperm morphology for pregnancy outcomes after intrauterine insemination (IUI) and controlled ovarian hyperstimulation (COH) in the presence of normal sperm concentration and motility. MATERIALS AND METHODS: A retrospective review of 42 couples undergoing COH/IUI was stratified by favorable or unfavorable sperm morphology. End points were pregnancy or failure of treatment as defined by four or more cycles of COH/ IUI without pregnancy. RESULTS: An unfavorable morphology (< 4%) was highly predictive of failure during COH-IUI (94.45%; 17/18). A normal PIF was a sensitive indicator of those patients who became pregnant (93.8%; 15/16) and had a fair specificity for failure to achieve pregnancy after four cycles of treatment (65.4%; 17/26). Couples with a favorable sperm morphology were 28.3 times as likely to achieve a pregnancy within four cycles of treatment as those with unfavorable sperm morphology [95% confidence limits, 3.2 to 250.5; P < 0.001]. CONCLUSIONS: Abnormal strict morphologic assessment is both sensitive and specific for pregnancy outcomes in couples undergoing COH/IUI. Couples with persistently unfavorable sperm morphology should be counseled appropriately and would be better served by more aggressive treatment with in vitro fertilization and embryo transfer.
Adult↗
Estimation of the progenitor cell yield in a leukapheresis product by previous measurement of CD34+ cells in the peripheral blood.
To assess whether measurement of CD34+ cells in the peripheral blood allows one to estimate the progenitor cell yields of subsequent leukapheresis procedures, 733 corresponding blood and leukapheresis samples were analyzed. Peripheral blood progenitor cells of cancer patients were mobilized with hematopoietic growth factors alone or postchemotherapy, and harvested processing 10 liters of blood for each leukapheresis product. The CD34+ cell count (CD34+ cells/microliter blood) correlated most closely with the progenitor cell yield in the corresponding leukapheresis product (CD34+ cells/kg bodyweight, r = 0.80), while the proportion of circulating CD34+ cells to the white blood and mononuclear cells predicted the yield less reliably (r = 0.74 and r = 0.60). The CD34+ cell yield was independent of the white blood count (r = 0.04), whereas a weak correlation was found between the mononuclear cell count and the number of CD34+ cells/kg collected (r = 0.42). It was unlikely to obtain the threshold quantity of 2.5 x 10(6) CD34+ cells/kg required for rapid engraftment when counts below 10 CD34+ cells/microliter blood were detected. At levels between 10 and 30 CD34+ cells/microliter sufficient autografts could be harvested, whereas 30-100 CD34+ cells/microliter were required to achieve this by a single leukapheresis. A surplus of CD34+ cells was likely above 100 CD34+ cells/microliter which could be useful for progenitor cell enrichment techniques. The correlation between the CD34+ cell count and progenitor cell yield was independent of the mobilizing regimen and whether leukaphereses had been performed previously. In conclusion, the number of CD34+ cells/microliter blood allows a reliable prediction of the CD34+ progenitor cell yield in subsequent leukapheresis procedures. However, rare cases of unexpectedly sufficient progenitor cell yields may be observed even at CD34+ cell levels below detection limit.
Adolescent↗
High-dose therapy with peripheral blood progenitor cell transplantation in low-grade non-Hodgkin's lymphoma.
It was the objective of our study to evaluate the efficacy of a sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support in patients with low-grade non-Hodgkin's lymphoma (NHL). Since July 1991, 48 patients (23 male/25 female) with a median age of 43 years (range 26-55) were included in the study. At the time of entry, 28 patients were in first and seven in second or higher remission. Twelve patients had relapse of disease and one patient had tumor progression. PBPC were collected during granulocyte colony-stimulating factor (G-CSF)-enhanced leukocyte recovery following treatment with high-dose cytarabine and mitoxantrone (HAM). A median of two leukaphereses (range 2-7) resulted in 6.9 x 10(6) CD34+ cells/kg (median, range 2.1 x 10(6)-38.8 x 10(6)). A comparison was made between the harvests obtained from patients in first remission and those from patients in second remission, in relapse or progressive disease. Patients mobilized in first remission tended to have a greater collection efficiency for CD34+ cells comprising a significantly greater proportion of more primitive CD34+/Thy-1+ progenitor cells. Conversely, leukapheresis (LP) products collected during first remission contained a significantly smaller proportion of CD34+/CD45RA+ cells and CD34+/c-kit+ cells, subsets which reflect a more differentiated progenitor cell stage. Following high-dose therapy and PBPC autografting, the median time to reach platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l and 12 and 13 days, respectively. Two patients died of treatment-related toxic organ failure. Thirty-nine patients are alive in remission after a median follow-up time of 15 months (range 1-31), while seven patients relapsed between 5 and 29 months post-transplantation. Except for one patient autografted in first remission, the patients with relapse had a history of previous relapse or progressive disease. Since the probability of disease-free survival appears to be related to the disease status at the time of autografting, PBPC-supported high-dose therapy including total body irradiation should be investigated further for patients with low-grade NHL while they are in first remission.
Adult↗
Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support.
A retrospective analysis of long-term hematopoiesis was performed in a group of 145 consecutive patients who had received high-dose therapy with peripheral blood progenitor cell (PBPC) support between May 1985 and December 1993. Twenty-two patients had acute myelogenous leukemia, nine had acute lymphoblastic leukemia, 43 had Hodgkin's disease, 57 had non-Hodgkin's lymphoma, and 14 patients had multiple myeloma. Eighty-four patients were male and 61 female, with a median age of 37 years (range, 16 to 58 years). In 46 patients, PBPC were collected after cytotoxic chemotherapy alone, while 99 patients received cytokines either during steady-state hematopoiesis or post-chemotherapy. Sixty patients were treated with dose-escalated polychemotherapy, and 85 patients had a conditioning therapy including hyperfractionated total body irradiation at a total dose of 14.4 Gy. The duration of severe pancytopenia posttransplantation was inversely related to the number of reinfused granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Threshold quantities of 2.5 x 10(6) CD34+ cells per kilogram or 12.0 x 10(4) CFU-GM per kilogram became evident and were associated with rapid neutrophil and platelet recovery within less than 18 and 14 days, respectively. These numbers were also predictive for long-term reconstitution, indicating that normal blood counts are likely to be achieved within less than 10 months after transplantation. Conversely, 12 patients were autografted with a median of 1.75 x 10(4) CFU-GM per kilogram resulting in delayed recovery to platelet counts of greater than 150 x 10(9)/L between 1 and 6 years. Our study includes bone marrow examinations in 50 patients performed at a median follow-up time of 10 months (range, 1 to 85 months) posttransplantation. A comparison with normal volunteers showed a 3.2-fold smaller proportion of bone marrow CD34+ cells, which was paralleled by an even more pronounced reduction in the plating efficiency of CFU-GM and burst-forming unit-erythroid. No secondary graft failure was observed, even in patients autografted with relatively low numbers of progenitor cells. This suggests that either the pretransplant regimens were not myeloablative, allowing autochthonous recovery, or that a small number of cells capable of perpetual self-renewal were included in the autograft products.
Adolescent↗
Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy.
Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic chemotherapy and cytokines. There is a substantial variability in the yield of hematopoietic progenitor cells between patients. We were looking for predictive parameters indicating a patient's response to a given mobilization regimen. Multiparameter flow-cytometry analysis and clonogenic assays were used to examine the hematopoietic progenitor cells in bone marrow (BM) and peripheral blood (PB) before filgrastim (R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in PB and leukapheresis products (LPs) in the recovery phase. Fifteen patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence plots showed a homogenous population of strongly CD34+ cells in steady-state and mobilized PB whereas in steady-state BM, the CD34+ cells ranged from strongly positive with continuous transition to the CD34- population. Consistent with the similarity in CD34 antigen expression, a correlation analysis showed steady-state PB CD34+ cells (r = .81, P < .001) and colony-forming cells (CFCs; r = .69, P < .01) to be a measure of a patient's mobilizable CD34+ cell pool. Individual estimates of progenitor cell yields could be calculated. With a probability of 95%, eg, 0.4 steady-state PB CD34+ cells x 10(6)/L allowed to collect in six LPs 2.5 x 10(6) CD34+ cells/kg, the reported threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR- subset nor the BM CFC count had a predictive value for the mobilization outcome. This may be caused by the additional presence of maturing progenitor cells in BM, which express lower levels of the CD34 antigen and do not circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.
Adult↗
Blood-derived autografts collected during granulocyte colony-stimulating factor-enhanced recovery are enriched with early Thy-1+ hematopoietic progenitor cells.
It was the objective of the study to characterize CD34+ hematopoietic progenitor cells from peripheral blood (PB) and bone marrow (BM) in a group of 24 cancer patients. After cytotoxic chemotherapy, R-metHu granulocyte colony-stimulating factor (R-metHuG-CSF; filgrastim, 300 micrograms daily, subcutaneously) was given to shorten the time of neutropenia as well as to increase the rebound of peripheral blood progenitor cells (PBPC) for harvesting. The proportion of CD34+ cells in the leukapheresis products (LPs) was 1.4-fold greater than in BM samples that were obtained at the same day (LP: median, 1.4% v BM: median, 1.0%, P < .01). Two- and three-color immunofluorescence showed that blood-derived CD34+ cells comprised a greater proportion of a particular early progenitor cell than CD34+ cells of bone marrow. Blood-derived progenitor cells tended to have a higher mean fluorescence intensity of CD34 and expressed significantly lower levels of HLA-DR (mean fluorescence intensity of HLA-DR: 442.6 +/- 44.9 [LP] v 661.5 +/- 64.6 [BM], mean +/- SEM, P < .01). Furthermore, the blood-derived CD34+ cells comprised a 1.7-fold greater proportion of Thy-1+ cells (LP: median, 24.4% v BM: median, 14.4%, P < .001) and expressed significantly less c-kit (LP: median, 20.5% v BM: median, 31.0%, P < .01). Three-color analysis showed that high levels of Thy-1 expression were restricted to CD34+/HLA-DRdim or CD34+/HLA-DR- cells confirming the early developmental stage of this progenitor cell subset. The proportion of CD34+/CD45RA(bright) cells representing late colony-forming unit granulocyte-macrophage (CFU-GM) was smaller in LPs compared with BM (P < .05). For an examination of BM CD34+ cells before the mobilization chemotherapy, samples of 16 patients were available. The mean proportion of c-kit expressing CD34+ cells in the bone marrow during G-CSF-stimulated reconstitution decreased 1.8-fold compared with baseline values. There was no difference in the proportion of BM-derived CD34+/Thy-1+ cells and CD34+/CD45RA+ cells between steady-state hematopoiesis and G-CSF-supported recovery. Our data suggest that during G-CSF-enhanced recovery, CD34+ cells in the PB are enriched with more primitive progenitor cells to evenly replenish the BM after the chemotherapy-related cytotoxic damage.
Adult↗
High-dose therapy with peripheral blood progenitor cell support in patients with non-Hodgkin's lymphoma.
Between September 1991 and April 1995, high-dose therapy with peripheral blood progenitor cell (PBPC) support was administered to 105 patients with non-Hodgkin's lymphoma (NHL). Thirty-three patients had high-grade NHL, while 72 patients had different forms of low- or intermediate-grade NHL. Except for three patients who received G-CSF during steady-state hematopoiesis, PBPCs were collected following cytokine-supported cytotoxic chemotherapy. This included G-CSF or the sequential administration of interleukin 3 (IL-3) and GM-CSF. Assessing bone marrow (BM) samples before the start of chemotherapy and leukapheresis (LP) products collected during cytokine-enhanced marrow recovery, a 2.3-fold greater mean concentration of CD34- cells was found in peripheral blood (p < 0.005). The blood-derived progenitor cells were enriched with a particular subset of more primitive progenitors, as the mean proportion of CD34+/Thy-1+ cells in LP products was three-fold greater in comparison to premobilization BM samples, respectively (p < 0.001). In contrast, the mean proportion of CD34+/CD19+ and CD19+ cells in LP products was 8.8- and 80-fold smaller compared to BM samples, respectively (p < 0.001). Following high-dose conditioning therapy including TBI in 74 patients, reinfusion of PBPC resulted in rapid and sustained engraftment in the majority of patients, while in seven patients an unsubstituted platelet count of greater than 20 x 10(9)/l was reached between 31 and 51 days. Five patients died of treatment-related complications between 13 and 188 days following transplantation. The probability of long-term disease-free survival at 30 months in patients autografted while they were in first remission was 70% in high-grade and 83% in low-grade NHL, respectively. The data may provide the rationale for the use of PBPC-supported high-dose regimens as first-line treatment for patients at high risk of treatment failure.
Adult↗
[Sequential high-dose therapy in patients with low-malignity non-Hodgkin's lymphoma].
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Antineoplastic Combined Chemotherapy Protocols↗
Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma.
For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.
Adolescent↗
Characterization of peripheral blood progenitor cells mobilized by cytotoxic chemotherapy and recombinant human granulocyte colony-stimulating factor.
The purpose of this study was to evaluate the antigenic profile of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and multiple myeloma (MM). The mobilization regimens consisted of high-dose cytarabine/mitoxantrone for patients with NHL, DexaBEAM for patients with HD, and high-dose cyclophosphamide (4 or 7 g per m2) for patients with MM. Cytotoxic therapy was supported by recombinant human G-CSF (Filgrastim, 300 micrograms/day sc) to shorten the period of neutropenia and to increase the number of circulating hematopoietic progenitor cells. The mean numbers of circulating CD34+ cells/microliters during leukocyte recovery were different between patient groups, 80.5 +/- 9.8 (mean +/- SEM) in low-grade NHL and 51.2 +/- 9.7 in high-grade NHL compared with 31.3 +/- 6.9 in HD and 24.4 +/- 4.1 in patients with MM. As a result, the greatest numbers of CD34+ cells/kg collected per leukapheresis were observed in patients with NHL, whereas the collection efficiency was substantially lower in patients with HD or MM. Patients with MM had also the smallest proportion of CD34+ cells in the mononuclear cell fraction (mean 0.79 +/- 0.10% versus 2.15 +/- 0.19% in low-grade NHL) but the greatest proportion of early CD34+ HLA-DR- progenitor cells (mean 2.38 +/- 0.51 versus 0.84 +/- 14% in low-grade NHL). Patients with MM had a mean proportion of CD34/c-kit+ cells that was twofold greater than that observed in patients with high- or low-grade NHL.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin's lymphoma.
PURPOSE: To evaluate the feasibility of a sequential high-dose therapy with peripheral-blood progenitor-cell (PBPC) support in patients with follicular lymphoma. PATIENTS AND METHODS: Since July 1991, we have included 30 patients (17 men and 13 women) with a median age of 41 years (range, 26 to 55) in the study. At the time of study entry, 17 patients were in first and six in second or higher remission. Another six patients had relapse of disease and one had tumor progression. PBPC were collected during filgrastim-supported leukocyte recovery following high-dose cytarabine (ara-C)/mitoxantrone (HAM). RESULTS: A median of two leukaphereses (range, one to seven) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 2.9 to 23.7 x 10(6). A distinct population of B-lymphoid progenitors (CD34+/CD19+) was not detectable in the autografts, and the content of CD19+ B cells was remarkably low, comprising a median of 0.07% of the mononuclear cells. Using the polymerase chain reaction (PCR) assay for the major breakpoint regions (MBR) of the bcl-2/immunoglobulin H (IgH) translocation, 22 patients had autografts positive for the t(14;18) translocation, whereas seven patients had PCR-negative transplants. The autograft of one patient could not be assessed. Following myeloablative therapy, hematologic recovery was rapid without cytokine support. The median times to reach a platelet count > or = 20 x 10(9)/L and neutrophil count > or = 0.5 x 10(9)/L were 11 and 13 days, respectively. Nonhematologic toxicity was moderate. Twenty-nine patients were alive in remission after a median follow-up duration of 6 months (range, 1 to 18). Of 22 patients autografted with t(14;18)-positive harvests, 11 had PCR-detectable cells in bone marrow and/or peripheral blood as long as 16 months posttransplantation. In contrast, six patients became PCR-negative between 3 and 16 months after reinfusion. Follow-up examinations with PCR data for the remaining five patients are not yet available. CONCLUSION: Conversion to PCR negativity in patients autografted with PCR-positive harvests suggests that the myeloablative regimen is effective and that any reinfused t(14;18)-positive cells may not be sustained. Because conventional chemotherapy provides no cure, we believe that high-dose therapy including total-body irradiation (TBI) should be explored in these particularly radiosensitive lymphomas.
Adult↗
Filgrastim post-chemotherapy mobilizes more CD34+ cells with a different antigenic profile compared with use during steady-state hematopoiesis.
For the mobilization of CD34+ peripheral blood progenitor cells (PBPC) filgrastim (R-metHuG-CSF) can be administered either during steady-state hematopoiesis or following cytotoxic chemotherapy. We compared both mobilization modalities intra-individually in seven patients with breast cancer. The number of circulating CD34+ cells was increased after filgrastim-supported chemotherapy compared with filgrastim administration during steady-state (on average, 129 vs. 19/microliters), resulting in a sevenfold higher yield of CD34+ cells per leukapheresis (5.73 vs. 0.79 x 10(6)/kg bodyweight). CD34+ PBPC harvested post-chemotherapy comprised a smaller proportion of early progenitor cells (CD34+/HLA-DR- or CD34+/CD38-) compared with filgrastim treatment alone. However, the absolute number of these early progenitor cells harvested was fivefold higher. The filgrastim-supported rebound after chemotherapy was characterized by a greater proportion of CD34+/CD33+ cells. Correspondingly, CD34+ PBPC mobilized post-chemotherapy contained a higher proportion of CFU-GM compared with filgrastim treatment during steady-state, while the cloning efficiency of CD34+ cells for BFU-E tended to be lower. Of note, the proportion of CD34+/CD19+ lymphoid progenitor and B cells was reduced after chemotherapy. In cancer patients, filgrastim mobilizes higher numbers of CD34+ cells when administered post-chemotherapy, compensating for the smaller proportion of early hematopoietic progenitors.
Adult↗
High-dose therapy and autografting with peripheral blood stem cells in malignant lymphoma: granulocyte-macrophage colony-stimulating factor for stem cell mobilization.
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Adult↗
Hematopoietic growth factors for the mobilization of peripheral blood stem cells.
Hematopoietic growth factors can be used for the mobilization of peripheral blood stem cells that have the proliferative capacity to restore long-term hematopoiesis after myeloablative therapy. An association between specific cytokines and the composition of the blood-derived progenitor cells has not yet emerged. It appears that yield and composition of PBSC are influenced far more by the individual than by the use of specific growth factors. Our future studies will focus on how many and what kind of stem cells are needed for high-dose regimens with different myelotoxicity. In parallel, autografts will be assessed for contaminating tumor cells, if disease- or clone-specific markers are available. This approach may then provide the rationale for the increasing use of PBSC for autografting.
Blood Cells↗
Autografting with peripheral blood stem cells mobilized by sequential interleukin-3/granulocyte-macrophage colony-stimulating factor following high-dose chemotherapy in non-Hodgkin's lymphoma.
This report summarizes our results of sequential treatment with IL-3 and GM-CSF following high-dose chemotherapy with respect to the yield and composition of peripheral blood stem cells (PBSC). Eight patients with high-grade non-Hodgkin's lymphoma were included in the study. Starting 24 h after high-dose cytosine arabinoside (Ara C)/mitoxantrone, IL-3 was given for 6 days, followed by GM-CSF. The increase of circulating hematopoietic progenitor cells during leukocyte recovery varied substantially from patient to patient. Up to a 22-fold interindividual difference was observed for the peak levels of CD34+ cells. A special focus of our study was the antigenic profile of the CD34+ PBSC. On analysis of the antigenic profile of the CD34+ cells, the proportion of CD34+/HLA-DR- and CD34+/CD38- cells representing non-committed hematopoietic stem cells was consistently < 5%. The vast majority of CD34+ cells was found to coexpress CD33 (86.3 +/- 2.1%, mean +/- SEM), reflecting myeloid lineage commitment. CD71 antigen was present on 47.4 +/- 3.0% CD34+ cells with two populations (CD71dim/bright), while the percentage of early B lymphoid (CD34+/CD19+) progenitor cells was extremely low (0.38 +/- 0.13%). We therefore conclude that the cytokines currently available such as G-CSF, GM-CSF or IL-3 facilitate an ontogenetic phenomenon supporting the redistribution of hematopoietic progenitor cells after cytotoxic treatment. Six patients were autografted with the IL-3/GM-CSF-exposed blood stem cells following high-dose conditioning therapy. It is worth noting that no additional BM or hematopoietic growth factors were given post-transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Increased serum levels of granulocyte colony-stimulating factor after autologous bone marrow or blood stem cell transplantation.
The objective of our study was to evaluate the biologic role of granulocyte colony-stimulating factor (G-CSF) for hematologic reconstitution following autologous bone marrow transplantation (ABSCT). Using a commercially available enzyme-linked immunosorbent assay, serum levels of G-CSF were measured in samples from 48 patients (30 male/18 female) who underwent ABMT or ABSCT. Their median age was 34.5 years (range 16 to 51). Autografting was performed (40 ABMT, 8 ABSCT) in 23 AML, 8 ALL and 17 malignant lymphoma patients. Patients transplanted with blood stem cells had a faster leukocyte and neutrophil recovery compared with the ABMT patients (p < 0.025 and p < 0.05, respectively). During marrow aplasia G-CSF serum levels were elevated in all patients, with a median peak value of 2199 pg/mL (range 453 to 8676 pg/mL). A strong reverse correlation (R = -0.76, p < 0.01) could be demonstrated between G-CSF serum level and white blood count (WBC). An additional increase of G-CSF serum levels on days of fever (> or = 38.5 degrees C) or documented infectious disease was observed. During the early phase of marrow aplasia, the endogenously produced amounts of G-CSF reached concentrations which are used for in vitro stimulation of colony-forming unit granulocyte (CFU-G). The relationship between G-CSF serum level and WBC supports the central role of this circulating hemopoietin following myeloablative treatment and autotransplantation. During periods of higher demand such as fever and infectious complications, endogenous G-CSF production is enhanced.
Adolescent↗
Idarubicin/cytosine arabinoside and mitoxantrone/etoposide for the treatment of de novo acute myelogenous leukemia.
Since January 1989, 56 patients (31 females and 25 males) with de novo acute myelogenous leukemia have been included in the study. Their median age was 43 years (range, 15 to 60 years) with a distribution according to French-American-British morphologic subtypes as follows: six M1, 14 M2, four M3, 19 M4, nine M5, two M6, and two M7. The induction regimen (IDAC) consisted of idarubicin (12 mg/m2/d intravenously [IV] days 1 to 3) in combination with cytarabine (100 mg/m2/d continuous IV days 1 to 7). Patients achieving complete remission (CR) or partial remission received another cycle of IDAC followed by NOVE (mitoxantrone 10 mg/m2/d IV days 1 to 5 and etoposide 100 mg/m2/d IV days 1 to 5). Fifty-four patients are evaluable for response: after two cycles of IDAC, 42 patients had attained CR (78%), while 76% of these had already reached CR after the first cycle. Of the initial 11 nonresponders to IDAC, four obtained CR after NOVE. Thus, 46 of 54 patients (85%) achieved CR after sequential treatment with IDAC and NOVE. In the last 17 patients who entered CR or partial remission after the first cycle of IDAC, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 3 micrograms/kg/d) was administered for 6 days starting 3 days prior to the second cycle of IDAC. For consolidation with NOVE, rhGM-CSF was given according to the same dosage schedule. After 72 hours of rhGM-CSF treatment, the white blood cell count showed a median 3.9-fold increase, without appearance of myeloblasts in the peripheral blood. During sequential chemotherapy, no significant complications (in particular, no major cardiac toxicity) were observed. Postremission, patients were either given bone marrow transplants, received late consolidation with high-dose cytarabine/mitoxantrone, or were followed up without any further treatment. Of the 46 patients evaluable for disease-free survival, 21 patients (45%) remain in CR with a 34% probability of disease-free survival at 37 months. The response-adapted treatment with IDAC/NOVE is effective and very well tolerated. To define the therapeutic impact of rhGM-CSF, a randomized trial will be required.
Acute Disease↗