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Macrophage response to viruses, protozoa, and fungi: secretory and cellular activities induced in resting unprimed bone marrow-derived mononuclear phagocytes.

The secretory (tumor necrosis factor, TNF-alpha; nitrite) and cellular response (mitochondrial respiration, TNF-alpha-independent tumoricidal activity) of a pure, lymphocyte-free population of resting, unprimed rat bone marrow-derived mononuclear phagocytes (BMM phi) to direct interaction with viruses, protozoa, and fungi was assessed and compared with that triggered by bacterial agents and interferon-gamma (IFN-gamma). Viruses (herpes simplex, vaccinia, poliomyelitis, vesicular stomatitis, lymphocytic choriomeningitis, Sendai), protozoa (Trypanosoma brucei, Giardia lamblia), and fungi (Penicillium, Trichosporon, Fusarium, Rhizopus, Aspergillus, Geotrichum species) affected primarily the secretion of TNF-alpha and mitochondrial respiration of BMM phi; their effects on the secretion of nitrite and on tumoricidal activity were at best marginal. Collectively, the macrophage response to viruses, protozoa, and fungi was less varied and less marked than that to bacterial agents (intact organisms, peptidoglycan, lipoteichoic acid, lipopolysaccharide) and IFN-gamma.

Animals↗

In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis.

One approach to resolving the complexities of chondrogenesis is to examine simplified systems in vitro. We analyzed cartilage differentiation by human adult stem cells from bone marrow stroma. Marrow stromal cells were cultured as micromass pellets for 21 days in serum-free medium containing transforming growth factor (TGF)-beta3, dexamethasone, and bone morphogenetic protein (BMP)-6. Assays for pulse-labeled [3H]DNA and for total DNA indicated that there was little proliferation and a progressive loss of cells in the pellets. There were continuous increases in mRNAs for cartilage matrix (proteoglycans and COL2, -9, -10, and -11), receptors [fibroblast growth factor 2 (FGFR2) and parathyroid hormone-related peptide receptor (PTHrP-R)], and transcription factors (SOX5, -6, and -9) as demonstrated by histochemical and microarray assays. Reverse transcription-PCR assays for 11 mRNAs confirmed the microarray data. SOX4, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 14 (MMP14) increased at day 1 and decreased thereafter, suggesting roles early in chondrogenesis. Also, forkhead, CD10, and MMP13 increased up to day 7 and decreased thereafter, suggesting roles in an intermediate stage of chondrogenesis. In addition, two collagens (COL3A1 and COL16A1), a signaling molecule (WNT11), a homeobox homolog (BAPX1), a receptor (IL-1R1), an IGFs modulator (IGFBP5), and a mettaloproteinase (MMP16) increased progressively up to about day 14, suggesting roles later in chondrogenesis. Our results indicate that the simplicity of the system makes it possible to define in detail the cellular and molecular events during chondrogenesis.

Adult↗

Co-administration of Flt-3 ligand counteracts the actions of thrombopoietin in myelosuppressed rhesus monkeys.

This placebo-controlled study evaluated the efficacy of Flt-3 ligand (FL) combined with TPO in myelosuppressed rhesus monkeys. The monkeys were subjected to 5 Gy total body irradiation (TBI), resulting in 3 weeks of profound pancytopenia, and received either 5 microg/kg of rhesus TPO i.v. on d 1 (n = 4) and 100 microg/kg/d s.c. human FL (n = 4) or FL alone (n = 4) for 14 consecutive days and were compared with results from a concomitant study involving the administration of TPO alone (n = 4) or placebo (carrier; n = 4). The TPO/FL combination was considerably less effective than TPO alone, with a more profound nadir and a slower recovery to thrombocyte counts > 100 x 109/l, approaching recovery patterns of placebo controls. Leucocyte regeneration was similar in all animals. Monkeys treated with FL alone displayed a regeneration of reticulocytes and thrombocytes in the lower range of those of the placebo controls. Recovery of bone marrow (BM) cellularity was slightly accelerated in the TPO/FL-treated monkeys, but was not reflected by an increase in progenitor cells, in contrast to TPO alone. Monkeys treated with FL alone showed a BM reconstitution similar to placebo-treated controls. FL by itself was not effective as a therapeutic agent in this model for myelosuppression. As FL also suppressed BM CD34+ cell reconstitution, we concluded that FL competed with TPO at the level of immature cell differentiation.

Animals↗

Recovery of normal hematopoietic tissue and tumor following chemotherapeutic injury from cyclophosphamide (CTX): comparative analysis of biochemical and clinical techniques.

Simultaneous alterations in the incorporation of 3H-thymidine (3H-TdR) into DNA are induced by CTX in normal host target tissues and L1210 ascites tumor. The timing of suppression and recovery of these nucleoside incorporation alterations was similar at the three CTX doses studied, but some evidence for a dose-response effect was seen as the magnitude of suppression of DNA synthesis increased with increasing dosage. A differential pattern of suppression and recovery of 3H-TdR incorporation in malignant and normal host tissues was observed. The pattern of suppression and recovery of the peripheral white blood count and bone marrow (BM) cellularity, two frequently studied clinical parameters of hematopoietic recovery, were out of phase with the recovery of BM-DNA synthesis and failed to accurately reflect the sensitivity of the BM to subsequent chemotherapeutic injury. In contrast, drug schedules based on the differential recovery patterns of the host tissues and tumor, reflected by their 3H-TdR incorporation into DNA, both reduced toxicity to normal mice and increased the survival of tumor-bearing animals.

Animals↗

Pluripotent stem cells constitutively expressing a normal erythropoietin receptor give rise to normal hematopoiesis in lethally irradiated recipient mice.

The cellular mechanism by which the stem cell differentiates toward an individual myeloid lineage is unknown. To determine whether lineage-specific cytokines are involved in stem cell determination, murine bone marrow cells were infected with a retroviral vector carrying a murine erythropoietin receptor (EpoR) cDNA. Infected marrow cells were transplanted into lethally irradiated syngeneic recipient mice, and the effect of Epo was studied on EpoR-expressing pluripotent stem cell determination. The graft contained, among myeloid cells, around 100 CFU-S12, half of which were retrovirally infected. One month after grafting, the bone marrow of mice reconstituted with EpoR-infected cells contained 50 times more infected multipotent progenitors than mice reconstituted with control bone marrow cells. However, this number returned to normal 45 days after the graft. No variation was observed in peripheral blood, bone marrow, and spleen cellularities or in committed progenitors in the bone marrow and in the spleen when Neo or EpoR reconstituted mice were assayed. When Epo was delivered into reconstituted mice one month after grafting, Epo had no differential effect in EpoR or Neo reconstituted mice. This study emphasizes the in vivo Epo proliferative response of multipotent progenitors expressing a normal EpoR gene and shows that, in vivo as in vitro, the differentiation of these multipotent progenitors is not preferentially oriented toward erythropoiesis.

Animals↗

Interferon alpha-2b as treatment for Philadelphia-negative chronic myeloproliferative disorders with excessive thrombocytosis.

We treated 32 patients with Ph1-negative chronic myeloproliferative disorders (CMD) with excessive thrombocytosis with Interferon alpha-2b (IFN alpha-2b): 26 had essential thrombocythaemia, ET (18 previously untreated, eight pretreated); one thrombocythaemia after treatment for Hodgkin's disease (HD); two thrombocythaemia associated with non-Hodgkin's lymphoma (NHL); three stage II idiopathic myelofibrosis (IM). IFN was given at daily doses of 1-4 x 10(6) IU. Twenty-seven patients (84%) responded, 17 (53%) achieved complete haematologic response after a median time of 12 weeks, and 10 (31%) partial haematologic response. Median platelet levels declined in complete haematologic response patients from 1,190 to 335 x 10(9)/l. Normalization of megakaryocyte (MK) levels was observed in 8/17 complete haematologic response patients treated for 9-12 months, with decreased bone marrow (BM) cellularity. Side effects requiring dose reduction or discontinuation of treatment occurred in 28% of cases with IFN doses of 2 or 4 x 10(6) IU. After 1 year of continuous IFN treatment, responses were maintained with conventional chemotherapy or low-dose IFN. This study demonstrates that IFN has definite therapeutic activity in CMD with excessive thrombocytosis. This biological agent, either alone or in combination with other antineoplastic treatment, may represent a new therapeutic approach for these disorders.

Adult↗

Successful treatment of incipient graft rejection with donor leukocyte infusions, further proof of a graft versus host lymphohaemopoietic effect.

Graft rejection is a major cause of treatment failure after T-cell-depleted stem cell transplantation (TCD-SCT) and remains a therapeutic challenge. Donor leukocyte infusions (DLIs) have an efficient graft versus host effect, which has been successfully used to treat recipient relapses. We hypothesized that this effect could be exploited to counteract the host versus graft reactions responsible for graft rejection. We report two adult patients with haematological malignancies who underwent sex-mismatched TCD-SCT from HLA-identical sibling donors. Peripheral blood (PB) counts and bone marrow (BM) cellularity were studied on a serial basis. Sequential chimaerism and minimal residual disease analysis were performed by FISH on PB and BM samples as well as on leukocyte lineages (T and B lymphocytes and myeloid cells) purified from PB using immunomagnetic technology. Both patients were diagnosed with incipient graft rejection 2-3 months after engraftment, based on persistently decreasing PB counts and BM cellularity together with the observation of decreasing mixed chimaerism (increasing percentage of recipient cells), mostly in whole PB and T lymphocytes. Both patients were successfully treated with a single DLI (1 x 10(7) CD3+ cells/kg), thereafter achieving normal PB counts and BM cellularity as well as complete chimaerism. Interestingly, the only side effect observed was mild graft versus host disease that did not require treatment. In conclusion, provided that an early diagnosis is made, the graft versus host lymphohaemopoietic effect harboured by immunocompetent donor cells can be successfully used for the treatment of incipient graft rejection.

Antigens, CD34↗

Pre-mRNA from erythroid enriched bone marrow cells of the rabbit.

Different fractions of cellular RNA from erythroid enriched bone marrow cells of the rabbit, extracted by the temperature fractionation method, were investigated by hybridization to globin cDNA. 97.4% of all globin sequences were found in the 4 degrees C franction (cytoplasmic RNA) 0.11% are in the 40 degrees / 50 degrees C fraction and 2.47% in the 65 degrees C and 85 degrees C franctions (pre-mRNA). This shows a substantial purification of the pre-mRNA fractions from cytoplasmic mRNA. 33% of the globin sequences in the 65 degrees C and 85 degrees C fractions are polyadenylated. The poly(A)+-RNA from the 65 degrees C and 85 degrees C fractions separated in a formamide sucrose gradient showed a clear hybridization to globin cDNA in the region between 9S and 28S and around 4S. In a control experiment in which RNA from baby hamster kidney cells (BHK) was mixed with globin mRNA and separated in the same manner hybridization was observed at the 9S position of the gradient only.

Animals↗

Suppressive effect of met-enkephalin on bone marrow cell proliferation in vitro shows circadian pattern and depends on the presence of adherent accessory cells.

The cellularity of femoral bone marrow and the content of the granulocyte-macrophage colony forming cells (GM-CFC) were followed in mice between 0600 h and 1800 h. The cellularity increased at the beginning of the light period, and the GM-CFC content at the end. Opioid pentapeptide methionine-enkephalin reduced the GM colony forming ability of the bone marrow cell suspensions in proportion to the GM-CFC content. Removal of the accessory cells reversed the enkephalin sensitivity pattern of the GM-CFC. The circadian variations have been ascribed to a neuroendocrine regulatory network involving the opioid peptides and affecting the bone marrow accessory cells. The work draws attention to the circadian activity pattern of hemoregulatory oligopeptides applicable as adjuvants to antineoplastic chemotherapy.

Analysis of Variance↗

Administration of recombinant human interleukin-7 to mice induces the exportation of myeloid progenitor cells from the bone marrow to peripheral sites.

The administration of recombinant human interleukin-7 (rhIL-7) to mice twice a day for 7 days does not appreciably change bone marrow (BM) cellularity, but does result in a threefold to fivefold increase in the total number of leukocytes in the spleen, an eightfold to 10-fold increase in the total number of nonparenchymal cells (NPC) obtained from the liver, and up to a 20-fold increase in the total number of peripheral white blood cells (WBC). This regimen of rhIL-7 administration also causes a profound reduction in the total number of progenitors in the BM for both single-lineage colony-forming units-culture (CFU-c) (> 90%) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM) (> 99%) colonies. In contrast, mice treated with rhIL-7 exhibited increases in both CFU-c (20- to 40-fold, 20-fold, and 15- to 40-fold) and CFU-GEMM (8- to 10-fold, 30-fold, and 6- to 10-fold) cultured from the peripheral blood, spleen, and NPC, respectively. The increase in CFU in the NPC was accompanied by a fivefold increase in the number of MAC-1+ cells and a ninefold increase in the number of 8C5bright+ cells. Splenectomy of mice before the administration of rhIL-7 further increased the total number of WBC, NPC, and myeloid progenitors as compared with the rhIL-7-treated nonsplenectomized mice. Finally, selective depletion of the BM by intraperitoneal administration of 89Sr (98% reduction in BM cellularity and > 99% reduction in BM myeloid progenitors) abrogated the rhIL-7-induced increases in cellularity and myeloid progenitor number in the peripheral blood, spleen, and NPC. These results show that the changes in myelopoiesis observed after in vivo administration of rhIL-7 to mice result largely from the emigration of myeloid progenitors from the BM through the blood to the spleen, liver, and, possibly, other peripheral organs.

Animals↗

In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: a phase I study.

PIXY321 is a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 micrograms/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P < .001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.

Agranulocytosis↗

The applicability of simple blood and bone marrow variables in prediction of acute leukaemia in patients with acquired bi- or pancytopenia.

A retrospective study of 44 patients presenting with acquired bi- or pancytopenia (B/PC) and no evidence of any causal disorder was carried out. 12 patients developed acute non-lymphoblastic leukaemia after 2-51 months. Compared to the nonleukaemic subjects the preleukaemic patients at the onset of B/PC had significantly higher counts of myeloblasts and other myelopoietic cells in the bone marrow, more cellular marrows due to more dense cellularities of all compartments, higher blood granulocyte and monocyte counts, more pronounced anisocytosis, and in some cases a small number of circulating myeloblasts. A stepwise multiple logistic regression analysis identified 3 combinations of variables displaying significant simultaneous association with subsequent leukaemic transformation. Among these the combination of marrow myeloblast percentage and blood granulocyte count might be applicable to early prospective identification of patients with preleukaemic B/PC.

Acute Disease↗

Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study.

We analyzed data from 388 subjects with Fanconi anemia reported to the International Fanconi Anemia Registry (IFAR). Of those, 332 developed hematologic abnormalities at a median age of 7 years (range, birth to 31 years). Actuarial risk of developing hematopoietic abnormalities was 98% (95% confidence interval, 93% to 99%) by 40 years of age. Common hematologic abnormalities were thrombocytopenia and pancytopenia. These were often associated with decreased bone marrow (BM) cellularity (75% of cases studied). Clonal cytogenetic abnormalities developed in 23 of 68 persons with BM failure who had adequate studies. Actuarial risk of clonal cytogenetic abnormalities during BM failure was 67% (47% to 87%) by 30 years of age. Fifty-nine subjects developed myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age. Risk was higher in persons with than in those without a prior clonal cytogenetic abnormality (3% [0% to 9%] v 35% [0% to 79%]; P = .006). One hundred twenty persons died of hematologic causes including BM failure, MDS or AML and treatment related complications. Actuarial risk of death from hematologic causes was 81% (67% to 90%) by 40 years of age.

Adolescent↗

Exact relevance of bone marrow cells in the healing process after myocardial infarction: analysis with a murine model of bone marrow cell transplantation.

BACKGROUND: Cellular cardiomyoplasty has created new possibilities in cardiac regeneration. Several cell types can be used in the procedure, such as skeletal myoblasts and bone marrow cells. Recent publications have suggested that bone marrow cells may be excellent candidates due to their pluripotency, but their actual role in cardiac regeneration is unknown. OBJECTIVE: To evaluate the exact physiological role of bone marrow cells in the healing process after myocardial infarction. METHODS: A mouse bone marrow cell transplantation model was used in which transplanted cells were easily detectable by immunohistochemistry. Chimeric mice were subjected to myocardial infarction by ligation of the left descending coronary artery. After one month, the mice were sacrificed and the scars were analyzed. RESULTS: Transplanted bone marrow cells were detected in the scars and these cells seemed able to transdifferentiate into endothelial cells, but no transdifferentiation into cardiomyocytes occurred. This mechanism of regeneration was dismissed because only 2% of the vessels in the scars were positive for transplanted cells. CONCLUSIONS: Bone marrow cells might be involved in myocardial healing, but this physiological mechanism is insufficient to allow correct regeneration.

Analysis of Variance↗

Modulation of murine pluripotential stem cell proliferation in vivo by lithium carbonate.

The effect of administering lithium in vivo on murine pluripotential stem cell proliferation was studied. Lithium was injected i.p. at various meq/liter concentrations (0.5-5.0 meq/liter). Data was obtained establishing that lithium increased the pluripotential stem cell population from normal mice as measured by the Till and McCulloch CFUs assay. Significant increases were demonstrated in: (1) bone marrow CFUs; (2) bone marrow organ cellularity, and (3) peripheral blood WBC. Marrow CFUs increase was maximum at 4 days post-lithium injection and greatest in the 1 meq/liter group (p < 0.001). Further increases in lithium concentration, i.e., 5 meq/liter, effectively reduced CFUs levels below normal, suggesting toxicity of the drug was apparent at this dose level. We conclude lithium may modulate granulopoiesis by increasing the CFUs stem cell compartment, thereby directly channeling differentiation into the granulopoietic pathway. This increases the committed progenitor stem cell (CFUc) population and ultimately peripheral blood end-stage cells.

Animals↗

[Experimental studies on the elimination of minimal residual leukemia in vivo by alternate half body irradiation].

The purpose of this study is to develop a new way for leukemia patients to tolerate an ablative chemoradiotherapy without BMT. Previous studies had demonstrated that only a few leukemia cells remained in the body during remission phase following chemotherapy and did not migrate to distant organs via the circulation until they had given rise to 3-4 x 10(5) new cells. The period required for such growth was about 20 days. However, hematopoietic stem cells migrate earlier than do leukemia cells. Therefore, alternate half body irradiation (HBI) within this period would kill the residual leukemia cells, but hematopoietic stem cells would migrate from shielded marrow to irradiated marrow and reconstruct hematopoiesis. BN rats were injected i.v. with 10 BNML subline LT12nl #15 cells, which had been transfected with the E. coli Lac-Z and Neo genes by retrovirus-mediated gene transfer. Cytochemical X-gal staining was used to identify the leukemia cells in agar culture. At day 9 after inoculation of leukemia cells, the rats were treated with cyclophosphamide (Cy 120 mg/kg), and 3 days later irradiated with 10 Gy (2 Gy/min, 6 MV, X-rays) on the upper half body, with the lower body shielded by a lead brick. They were then irradiated with the same dosage in the lower body with the upper half body shielded a week later. The preliminary results were as follow: At day 9 after inoculation, the cellularity of bone marrow (humerus, sternum, femur and tibia) was in the normal range, and the number of L-CFU ranged from 3.6 x 10(-5) to 9.0 x 10(-5) in agar culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transcoronary delivery of bone marrow cells to the infarcted murine myocardium: feasibility, cellular kinetics, and improvement in cardiac function.

Efficient strategies for labelling and delivery of bone marrow derived stem cells (BMCs) are required to elucidate the cellular kinetics and therapeutic effects after BMC transfer for myocardial infarction (MI). Lineage negative (lin-) BMCs, labelled ex vivo in a simple procedure with the cell tracker dye tetramethyl-rhodamine (TAMRA), were reliably detected by fluorescence microscopy with higher specificity than retroviral enhanced green fluorescence protein (EGFP) marking and detection. Only few cells entered the ischemic myocardium after intravenous (i.v.) application, but this number increased more than 18-fold after transcoronary delivery. Time course and kinetic analysis over 12 h revealed that myocardial colonization seems to be a biphasic process of first order decay with different elimination half-lives. Most cells are eliminated rapidly during the first 2 h (t1/2 40 min), but the remaining cells are retained significantly longer in the ischemic heart (t1/2 5.2 h). In contrast, BMC colonization of the spleen increased rather in a linear fashion. Although transcoronary BMC transfusion did not alter infarct size, it increased capillary density in the infarct border zone and improved LV function 4 weeks after MI. In conclusion, BMCs delivered by transcoronary injection increase capillary density and improve LV function after MI although homing to the ischemic heart is only transient.

Animals↗

Effects of short-term in vivo administration of G-CSF on bone marrow prior to harvesting.

The brief administration of G-CSF to previously treated solid tumor patients has a positive impact on the overall cellularity and progenitor cell content of harvested bone marrow. Fifty-seven patients, fully recovered from therapy and growth factor support, had approximately 500 mL of steady-state marrow harvested as outpatients under local anesthesia. Each patient then received 5 micrograms/kg of G-CSF every 12 hours subcutaneously for either 24 hours (21 patients), 36 hours (20 patients), or 48 hours (16 patients) just before harvesting 500 mL of activated bone marrow. Bone marrow cellularity (x 10(6)/mL) increased from a steady-state mean of 10.7 (+/- 0.9) to 25.7 (+/- 2.8) after 24 hours, 9.3 (+/- 0.7) to 29 (+/- 2.5) after 36 hours, and 9.6 (+/- 0.7) to 28.4 (+/- 2.5) after 48 hours. Although the percentage of CD34+ cells did not significantly change in stimulated marrow, the total number of CD34+ cells (x 10(6)) collected increased from 34 (+/- 6.3) to 52 (+/- 6.6) after two injections, 28 (+/- 3.6) to 65 (+/- 8.5) after three injections, and 28 (+/- 5.4) to 75 (+/- 18) after four injections of G-CSF. Further phenotyping demonstrated significant increases in CD34+HLA-DR+ cells with all three schedules relative to steady-state marrow. There were no changes in the total number of CD34+HLA-DR- cells after two and four shots; however, this population increased from 10 x 10(6) in steady-state marrow to 23 x 10(6) (p = 0.012) after three injections. Analysis of peripheral blood indicated a statistically significant increase in the circulating white count, but more interestingly, there were significant increases in the number of CD34+ cells x 10(4)/mL, suggesting the onset of mobilization. Steady-state blood contained a mean of 0.86 x 10(4)/mL CD34+ cells, which increased to 4.37 x 10(4)/mL, 7.43 x 10(4)/mL, and 8.62 x 10(4)/mL after two, three, and four injections, respectively-levels of CD34+ cells that are comparable to steady-state marrow. Reinfusion of a median of 1.6 x 10(6) activated CD34+ cells/kg resulted in the recovery of > 100/mm3 neutrophils and > 20,000 platelets by days 9 and 19, respectively, which was faster than our previous patients who received steady-state marrow, and comparable to our patients who received mobilized peripheral stem cells.

Adult↗