Biomedical subjects

A D Ho

Publications and source records attributed to A D Ho.

At least 73 records · Page 4Linked to original sources

PubMed2001

Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging.

The aim of our study was to investigate the quantitative microcirculation parameters amplitude A (hypothetical intravascular volume) and exchange rate constant k(21) (hypothetical vascular permeability) by contrast-enhanced dynamic magnetic resonance imaging (dMRI) as markers of angiogenesis in multiple myeloma (MM). Therefore lumbar spine and spina iliaca superior posterior of 16 normal controls and 41 patients with active MM were assessed using a dMRI protocol with a pump controlled bolus infusion of Gadolinium-DTPA. Pharmacokinetic parameters, amplitude A and exchange rate constant k(21) were calculated according to a 2-compartment model. Color-coded parameter images were generated from pharmacokinetic data analysis and superimposed onto the conventional MR images. Amplitude A and k(21) parameters were significantly increased in patients with MM compared with controls (p = 0.001; median A(ctr), 0.2 [range, 0.09-0.4]; median A(MM), 0.93 [range, 0.2-2.2]; median k(21ctr), 0.09 min(-1) [range, 0.03-0.9]; median k(21MM), 4.58 [range, 0.22-23.8]). Within the group of MM patients the pattern of color-coded parameter images were found to be either of "diffuse" (n = 13, 31%) or "focal" (n = 28, 69%) type of distribution of microcirculation. Comparison of amplitude A in patients with "focal" vs. "diffuse" pattern of the pharmacokinetic maps revealed a significant increase in the median of amplitude A in the "focal" group. Amplitude A values allowed a classification of patients according to severe osteolytic bone involvement (p = 0.023) with the best cutoff value of 0.7 for amplitude A. Downmodulation of amplitude A was observed in a MM patient treated with standard VAD chemotherapy. Our data demonstrate that dMRI is a novel imaging technique for the detection and monitoring of MM bone lesions. It provides independent evidence for angiogenesis in MM.

Adult↗

PubMed2001

Pilot study of hepatic intraarterial fotemustine chemotherapy for liver metastases from uveal melanoma: a single-center experience with seven patients.

BACKGROUND: Uveal melanoma is characterized by a high frequency of hepatic metastases. For patients with liver metastases, who have a median survival of 5 to 7 months, surgery and systemic conventional chemotherapy have little to offer. METHODS: Between February 1995 and July 1999, seven patients with isolated hepatic metastases from uveal melanoma were enrolled into a pilot trial of intraarterial fotemustine therapy. An implantable Port-A-Cath catheter was inserted into the hepatic artery for regional chemotherapy via the gastroduodenal artery. Fotemustine 100 mg/m2 was administered intraarterially over a 4-h period. The induction phase consisted of one administration per week for 4 weeks, followed by a 5-week rest period. Maintenance therapy with administration of fotemustine every 3 weeks continued until progression or toxicity. RESULTS: Ten patients were evaluated for the trial. One patient was not eligible because of impaired liver function, and in two patients implantation of the port system was not possible for anatomic reasons. Seven patients received a median of 16 treatment cycles (range, 4-28) and all were evaluable for response. Two patients achieved a partial response (PR), three had stable disease (SD), and tumor progressed in two patients (PD). The median survival time from diagnosis of liver metastasis was 24 months (range, 4 to 50+ months). Two patients survived for more than 2 years and two patients are still alive. The toxicity was low and the treatment could be administered on an outpatient basis. CONCLUSION: Intraarterial fotemustine treatment of uveal melanoma metastatic to the liver is well tolerated, and in some patients is associated with prolonged survival.

Adult↗

PubMed2001

Pulmonary artery hypertension during interferon-alpha therapy for chronic myelogenous leukemia.

In the conventionally treated group of patients with chronic myelogenous leukemia (CML) the prognosis has been significantly improved by interferon-alpha (IFN-alpha). Several side effects in association with IFN-alpha treatment have been reported. Here we present the first case of a CML patient with reversible pulmonary artery hypertension (PAH) during IFN-alpha therapy. The patient received IFN-alpha-2b (up to 10 million U/day) for 6 months until he started to complain of dyspnea on exertion and an afebrile non-productive cough. An echocardiography and right heart catheterization showed signs of right heart failure with PAH (80 mmHg). A reduced carbon monoxide diffusion capacity and partial respiratory insufficiency were noted. Inflammatory markers were not elevated and pulmonary infiltrates could not be detected. Respiratory infections, thromboembolic causes or autoimmune diseases were carefully ruled out. IFN-alpha was suspected as causative agent, because experimental investigations in sheep showed that IFN-alpha can stimulate the thromboxane cascade which resulted in transient PAH. A reduced pulmonary diffusion capacity had been observed secondary to PAH. After discontinuation of IFN-alpha, our patient's clinical status improved rapidly. After 6 months the pulmonary artery pressure had returned to near normal values (35 mmHg) and the pulmonary diffusion capacity was normal. It took one year until the electrocardiogram reverted to the pre-IFN-alpha pattern. PAH should be included in the differential diagnosis of patients treated with IFN-alpha who complain of exertional dyspnea in the absence of inflammatory signs.

Adult↗

PubMed2001

A man with hereditary exostoses and high-grade non-Hodgkin's lymphoma of the bone.

Multiple cartilaginous exostoses (MCE) is an autosomal dominant disorder that can lead to malignant transformation from exostoses to a secondary chondrosarcoma. We present a case report of a 52-year-old man with MCE who had a palpable mass at the left shoulder. At the site of the left proximal humerus, a cartilaginous exostosis was localized, suggesting that the tumor developed by a malignant transformation of an exostosis into a secondary chondrosarcoma. Interestingly, a biopsy showed a diffuse large B-cell lymphoma with Burkitt-like features. To our knowledge, the association of high-grade lymphoma and hereditary exostoses has not been described previously. This case demonstrates that a malignant tumor at the location of a cartilaginous exostosis is not necessarily a chondrosarcoma and that a biopsy is an essential part of the diagnostic work-up.

Bone Neoplasms↗

PubMed2001

Outpatient treatment of multiple myeloma with a combination of vincristine, Adriamycin and dexamethasone.

Patients with relapsed multiple myeloma (MM) have been shown to respond to a combination therapy consisting of vincristine, Adriamycin (doxorubicin) and high-dose dexamethasone (VAD). Because of the low hematological toxicity of the VAD regimen, this combination is frequently chosen for tumor reduction prior to high-dose therapy and blood stem cell transplantation. This study was designed to examine the efficacy and complications of outpatient VAD treatment. Over a period of 6 years, 103 outpatients with MM were treated with VAD chemotherapy administered by microprocessor-controlled infusion pumps via intravenous polyurethane catheters equipped with a safety valve. Response to treatment, treatment-associated complications and infections were documented and analyzed. In 85 of the 103 patients, tumor reduction by more than 25% was found. In 8 patients an occlusion occurred as a result of kinking of the central venous catheter in the subcutaneous segment. In two treatment cycles the infusions had to be stopped because of irreversible catheter occlusion. Twenty patients were hospitalized because of complications, which were infectious in 12 and noninfectious in 8. Severe infectious complications (> or =WHO grade III) occurred in 5.6% of the treatment cycles. Thus, continuous infusion of VAD over 96 h can be performed on an outpatient basis with a low complication rate.

Adult↗

PubMed2001

Infectious complications in chronic lymphoid malignancy.

Taking steps to minimize, prevent, and treat infection in patients with chronic lymphoid malignancies, especially chronic lymphocytic leukemia, has always been a challenge. As more patients with these diseases live longer and lead productive lives upon successful initial treatment, strategies for preventing infections have become more important. Distinguishing patients at low risk for infection from those at high risk is a crucial but challenging issue. Unfortunately, there are hardly any data on the use of prophylactic antibiotics for patients with chronic lymphoid malignancy (CLL). If patients cannot be enrolled in a clinical trial, antibiotics with co-trimoxazole should be administered when steroids are warranted. They should also be administered in patients who have had a documented infection early in the treatment course and during neutropenia. Viral infections remain another controversial issue in patients with CLL receiving treatment, especially a purine analogue. Very low CD4 counts (less than 50 cells/mL) might predict for reactivation for herpes zoster. Outside of depleted CD4 counts, there are no other means of identifying a high-risk group. Based on limited data, it would be reasonable to administer herpes zoster prophylaxis to patients with CD4 counts that are severely depleted or to patients with a prior episode of zoster. Controversial issues still remain regarding immunoglobulin treatment, specifically cost, scarcity of the product, and adequate dose, which has not yet been established. We would consider intravenous immunoglobulin (Ig) replacement in patients with marked hypogammaglobulinemia (IgG less than 400 mg/dL) with more than two recent severe infections [1]. Lower Ig doses (240 mg/kg) have been shown to be equivalent to higher ones in this trial [1].

Anti-Infective Agents↗

PubMed2001

Tandem high-dose chemotherapy in high-risk primary breast cancer: a multivariate analysis and a matched-pair comparison with standard-dose chemotherapy.

Stem cell-supported high-dose chemotherapy (HDCT) is currently being evaluated in patients with high-risk primary breast cancer (HRPBC), as defined by extensive axillary lymph node involvement. Conclusive results from randomized studies with sufficient patient numbers and follow-up are pending. We retrospectively analyzed 144 HRPBC patients enrolled in a single-arm trial of tandem HDCT at the University of Heidelberg to evaluate the prognostic value of nodal ratio, HER2/neu status, and cytokeratin-positive bone marrow cells and to compare the outcomes of these patients with those of a conventionally treated control group of 91 patients matched by nodal ratio, tumor size, combined hormone-receptor status, and HER2/neu status. The tandem HDCT regimen consisted of 2 cycles of induction chemotherapy followed by 2 cycles of blood stem cell-supported high-dose ifosfamide, 12 g/m2; carboplatin, 900 mg/M2; and epirubicin, 180 mg/m2. Conventionally treated patients received a regimen containing anthracycline without taxanes (52 patients) or CMF (cyclophosphamide, methotrexate, and 5-flurouracil; 39 patients). With a median follow-up of 3.8 years, disease-free, distant disease-free, and overall survival rates were 62%, 65%, and 84%, respectively. In univariate analysis, besides the hormone receptor status (P = .007), HER2/neu overexpression was the strongest predictor of earlier death (P = .017). In multivariate analysis, a nodal ratio of > or =0.8 was found to be the only independent predictor of relapse (relative risk [RR] = 2.09; 95% confidence interval [CI], 1.21-3.60; P = .008) and only the absence of hormone receptors was associated with earlier death (RR = 3.59; 95% CI, 1.45-8.86; P = .006). Despite a trend toward later distant relapse after HDCT compared with standard-dose chemotherapy with a median follow-up of 3 years (P = .059), thus far, matched-pair analysis has not demonstrated significantly better survival rates after HDCT in all matched patients (P = .786) or in the subgroups of anthracycline-treated patients and patients with and without overexpression of HER2/neu. So far, the follow-up time has been too short to draw definite conclusions; however, patients with a nodal ratio of > or =0.8, receptor-negative tumors, or HER2/neu overexpression are at high risk for relapse and death, irrespective of the kind of adjuvant chemotherapy.

Adolescent↗

PubMed2001

Molecular monitoring of the tumor load predicts progressive disease in patients with multiple myeloma after high-dose therapy with autologous peripheral blood stem cell transplantation.

The clinical relevance of the assessment of minimal residual disease (MRD) in patients with multiple myeloma (MM) to predict disease recurrence has not been proven. In the present study, we retrospectively analyzed the tumor load in peripheral blood (PB) and bone marrow (BM) samples of 13 patients with MM both in remission after high-dose therapy (HDT) with autologous PBSC transplantation (PBSCT) and at the time of progressive disease (PD). For six patients, subsequent samples obtained in remission could be included in the study. Tumor cells were assessed by means of quantitative PCR with allele-specific oligonucleotides (ASO-qPCR) based on the method of limiting dilutions. PD was documented with ASO-qPCR in BM samples (median concentration of tumor cells in remission vs at PD: 0.18% vs 4.6%) representing a significant increase by a median factor of 8.7. In PB, the median tumor load was 799 cells/ml in remission and 23 400 cells/ml at PD. With a median factor of 45, the increase was much more pronounced. Comparing the results of the molecular monitoring in PB with those of the determination of the monoclonal protein, routinely applied as parameter for the course of the disease, revealed a superiority of the molecular monitoring because of the significantly higher increase in the tumor load. Analyzing the subsequent remission samples showed an increase of the malignant cells in four out of six PB samples and in all four BM samples available, indicating the potential of ASO-qPCR for an early PD recognition.

Adult↗

PubMed2001

The FBMD-1 stroma cell line secretes a unique moiety which can increase retroviral transduction of lineage-committed and primitive human peripheral blood progenitor cells.

Peripheral blood progenitor cells are a prime target for gene therapy approaches. As recent data point to the relevance of soluble stroma factors for the efficient transduction of progenitor cells, we tested the stroma-conditioned medium (SCM) of the two cell lines FBMD-1 and L88/5 as well as desulfated and O-sulfated heparin (HS dS and HS OS) for their effect on transduction of peripheral blood progenitor cells. We transduced CD34+ cells of nine tumor patients with the retroviral SF-MDR vector containing the human multidrug resistance 1 (MDR1) gene under serum-free conditions on the fibronectin fragment CH-296 with or without SCM. Provirus-specific polymerase chain reaction showed a median 1.6-fold higher integration rate of the transgene into committed progenitor cells for the group with added FBMD-1 SCM (P=.008). This was maintained after 2 (P=.02) and, as a trend, after 5 weeks of stroma-dependent long-term culture. We found a median 1.5-fold increase in rhodamine-123 (Rh-123) exclusion in myeloid lineage-committed progeny cells following transduction in the presence of FBMD-1 SCM (P=.0004). After 2 or 5 weeks of long-term culture, a significantly higher proportion of Rh-123(dull) cells could still be detected in the FBMD-1 SCM transduction group (P=.003 and P=.04, respectively). L88/5 SCM or HS OS or HS dS was not effective as supplement for improving gene transfer. The FBMD-1 stroma cell line appears to secrete a unique moiety, which can increase retroviral transduction of lineage-committed and primitive progenitor cells. The FBMD-1 stroma activity is not attributable to heparan sulfate.

Adolescent↗

PubMed2001

Continuous complete remission in adult patients with acute lymphocytic leukaemia at a median observation of 12 years after autologous bone marrow transplantation.

We report our long-term experience with autologous bone marrow transplantation (ABMT) for 32 adult patients with acute lymphocytic leukaemia (ALL) in second or later remission (CR), or in first CR but with high-risk. Bone marrow was purged with mafosfamide (n = 25) or with immunomagnetic beads and monoclonal antibodies (n = 7). Retrospective analysis showed that 12 out of 32 patients were in continuous complete remission (CCR) at a median of 143 months (range 66-181 months). A plateau was reached at 50 months and the disease-free and overall survival rates were both 37.5%. It was notable that durable CCR could be achieved for patients in second (three out of nine) or third (one out of six) CR. ABMT could produce durable CCR and the long-term outcome compared favourably with those reported for allogeneic transplantation.

Adolescent↗

PubMed2001

Response to thalidomide in progressive multiple myeloma is not mediated by inhibition of angiogenic cytokine secretion.

Thalidomide (Thal) is a drug with anti-angiogenic properties. To explore whether the effect of Thal on angiogenesis is associated with a reduction of angiogenic cytokine levels in progressive multiple myeloma (MM), plasma levels of basic fibroblast growth factor, vascular endothelial growth factor, interleukin 6, tumour necrosis factor-alpha and hepatocyte growth factor (HGF) were measured in 51 patients at 0, 3 and 6 months of Thal therapy. After 6 months of treatment, 26 patients were considered to be responsive to Thal therapy, including 17 minimal responses, eight partial responses and one complete response. Only HGF (decreasing, P = 0.02) in the group of responsive patients showed a statistically significant change over a period of 6 months. Because HGF levels are known to correlate to MM tumour burden, we conclude that the mechanism of action of Thal in MM is not caused by a specific inhibition of angiogenic cytokine secretion.

Adult↗

PubMed2001

Divisional history and pluripotency of human hematopoietic stem cells.

To maintain self-renewal and multilineage differentiation capacity, hematopoietic stem cell (HSC) proliferation requires both symmetric and asymmetric cell divisions. We have applied a time-lapse camera system and our single-cell culture to correlate early replication behavior with short- and long-term function. Using five-dimensional flow cytometry to purify subpopulations of fetal liver (FLV), fetal bone marrow (FBM), umbilical cord blood (UCB), adult bone marrow (ABM), and mobilized peripheral blood (MPB), we studied the relationship between colony efficiency (CE) growth pattern and ontogenic age. The highest CE was found among HSC candidates from FLV, FBM, and UCB and the lowest from ABM. Relating the divisional behavior with functional readouts, we demonstrated that although mitotic rate, colony efficiency, and percent of asymmetric divisions all decreased with ontogenic age, the fraction of cells undergoing asymmetric divisions was consistently at 45%. After 10 days of culture, 60.6 +/- 9.8% of the PKH bright cells gave rise to colonies (15.8 +/- 7.8% dispersed) compared to 15.9 +/- 11.1% of the PKH dim cells (2.5 +/- 2.5% dispersed). In addition, the much more primitive Myeloid-Lymphoid Initiating Cells (ML-IC) are predominantly found in the PKH-bright population. Thus, primitive function of individual candidate HSCs closely related to their divisional behavior.

Antigens, CD34↗

PubMed2001

Centrosome aberrations and cancer.

Karyotypic alterations, including whole chromosome loss or gain, ploidy changes, and a variety of chromosome aberrations are common in cancer cells. If proliferating cells fail to coordinate centrosome duplication with DNA replication, this will inevitably lead to a change in ploidy, and the formation of monopolar or multipolar spindles will generally provoke abnormal segregation of chromosomes. Indeed, it has long been recognized that errors in the centrosome duplication cycle may be an important cause of aneuploidy and thus contribute to cancer formation. This view has recently received fresh impetus with the description of supernumerary centrosomes in almost all solid human tumors. As the primary microtubule organizing center of most eukaryotic cells, the centrosome assures symmetry and bipolarity of the cell division process, a function that is essential for accurate chromosome segregation. Centrosomes undergo duplication precisely once before cell division. Recent reports have revealed that this process is linked to the cell division cycle via cyclin-dependent kinase (cdk) 2 activity that couples centriole duplication to the onset of DNA replication at the G(1)/S phase transition. Alterations of regulatory G(1)/S phase proteins like the retinoblastoma protein, cyclins D and E, cdk4 and 6, cdk inhibitors p16( INK4A ) and p15( INK4B ), and p53 are among the most frequent aberrations observed in human malignancies. These alterations might not only lead to unrestrained proliferation but also cause karyotypic instability by uncontrolled centrosome replication. Since several excellent reports on cell cycle regulation and cancer have been published, this review will focus on causes and consequences of aberrant centrosome replication in human neoplasias.

Aneuploidy↗

PubMed2001

Successful treatment of bronchiolitis obliterans organizing pneumonia with low-dose methotrexate in a patient with Hodgkin's disease.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a rare disease, which is histopathologically defined by the presence of granulation tissue in the bronchioles, alveolar ducts and alveoli leading to plugging of the bronchiolar and alveolar lumen. BOOP is considered as a nonspecific response to many types of lung injury, including drugs, radiation, an underlying hematologic malignant neoplasm, autoimmune diseases, bacterial or virus infection, or an underlying lung disease, or occurs idiopathically. BOOP is mainly treated with corticosteroids, which induce a rapid clinical improvement. A frequent problem is relapse of disease when corticosteroid dosage is tapered off. We present the case of a 20-year-old patient with Hodgkin's disease developing BOOP after chemotherapy (COPP/ABVD) and irradiation. Initially, she responded well to corticosteroids, but relapsed when medication was discontinued. Complete remission of BOOP was achieved by long-term treatment with low-dose methotrexate (5-20 mg/week, i.v.).

Adult↗

PubMed2001

Comparison of double and triple high-dose chemotherapy with autologous blood stem cell transplantation in patients with metastatic breast cancer.

In patients with metastatic breast cancer (MBC), early dose intensification with multiple cycles of peripheral blood stem cell-supported high-dose chemotherapy (HDCT) seems superior to a late dose-intensification strategy. We compared the progression-free survival (PFS) and overall survival (OS) of 20 patients treated with a double (D)-HDCT regimen to 20 patients who received a triple (T)-HDCT, matched by age, estrogen receptor (ER) status, adjuvant chemotherapy, initial disease-free interval, predominant metastatic site, and number of metastatic sites. At a median follow-up of 41.5 months (range, 14-88 months) an intent-to-treat analysis showed no difference in PFS (p = 0.72) and OS (p = 0.93) between the matched patients. For all 76 patients treated within the D- or T-HDCT trial, median PFS and OS was 13 months (range, 2-78 months) and 24.5 months (range, 7-78 months), respectively. In multivariate analysis independent predictors of shorter OS included negative ER (relative risk [RR] = 3.0 [95% confidence interval (CI) 1.5-5.9]; p = 0.002), more than two metastatic sites (RR = 2.4 [95% CI 1.0-5.7]; p = 0.049) and failure to achieve complete remission/no evidence of disease (CR/NED) after HDCT (RR = 4.5 [95% CI 2.0-10.1]; p < 0.0001). These data show that early dose intensification with T-HDCT is not superior to a D-HDCT regimen in patients with MBC. ER-negative tumors, more than two metastatic sites and no CR/NED after HDCT, are associated with inferior outcome.

Adult↗

PubMed2001

Remarkable response to rituximab in a 72-year-old patient with refractory non-Hodgkin's lymphoma and marrow aplasia.

The chimeric human mouse antibody rituximab represents a substantial advance over the use of unmodified murine antibodies. Multicenter trials showed that rituximab induced remission in 48% of 166 relapsed lymphoma patients with minimal toxicity. Thus, the antibody might play a role in patients who cannot tolerate chemotherapy because of marrow aplasia. We observed a continuous complete remission induced by rituximab alone in a 72 year old patients with refractory and progressive high-grade non-Hodgkin's lymphoma (NHL) in the phase of chemotherapy induced marrow aplasia.

Aged↗

PubMed2001

High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma.

The aim of this study was to define prognostic factors that might be predictive for response to thalidomide (Thal) in progressive multiple myeloma (n = 54). We examined the concentration of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), two potent heparin-binding mediators of angiogenesis in peripheral blood (PB; PB-VEGF and PB-bFGF) and bone marrow (BM; BM-VEGF and BM-bFGF), in combination with well-characterized predictors for response and survival to chemotherapy. After a median follow-up time of 15 months (range, 0.3-20), 29 patients (pts.) showed at least a minimal response to Thal therapy, whereas 25 pts. were nonresponsive. As shown by univariate analysis, responsive pts. had statistically significant higher concentrations of PB-bFGF (P = 0.009) and beta2-microglobulin (P = 0.03) before therapy, as well as lower hemoglobin (P = 0.008) and albumin (P = 0.02) levels, whereas no statistically significant difference was found for PB-VEGF (P = 0.93). When a multiple logistic regression analysis was performed, PB-bFGF was the only statistically significant predictor for response to therapy (P = 0.01). None of these variables was associated with a prolonged progression-free survival. In conclusion, our findings indicate that high pretreatment plasma bFGF levels in pts. with progressive multiple myeloma are associated with unfavorable parameters of response and survival but nevertheless predict for response to Thal therapy.

Adult↗

PubMed2000

Microchimerism in bone marrow-derived CD34(+) cells of patients after liver transplantation.

Lymphoid and dendritic cells of donor origin can be detected in the recipient several years after a solid organ transplantation. This phenomenon is termed microchimerism and could play a role in the induction of tolerance. The fate of other hematopoietic cells transferred by liver transplantation, in particular of stem and progenitor cells, is unknown. For this reason, we studied peripheral blood and bone marrow samples of 12 patients who had received a liver transplant from an HLA-DR mismatched donor. Eight patients were long-term survivors between 2.8 and 10.1 years after allografting. CD34(+) cells from bone marrow were highly enriched with the use of a 2-step method, and a nested polymerase chain reaction was applied to detect donor cells on the basis of allelic differences of the HLA-DRB1 gene. Rigorous controls with DRB1 specificities equal to the donor and host were included. In 5 of 8 long-term liver recipients, donor-specific CD34(+) cells could be detected in bone marrow. Microchimerism in the CD34(+) cell fraction did not correlate to the chimeric status in peripheral blood. In conclusion, our results demonstrate a frequent microchimerism among bone marrow-derived CD34(+) cells after liver transplantation. The functional role of this phenomenon still needs to be defined. (Blood. 2000;96:763-767)

Adolescent↗