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Anthony D Ho

Publications and source records attributed to Anthony D Ho.

At least 73 records · Page 4Linked to original sources
PubMed2003

Successful treatment of a patient with hairy cell leukemia and pentostatin-induced autoimmune thrombocytopenia with rituximab.

The treatment of choice for hairy cell leukemia (HCL) are the purine analogs pentostatin and cladribine. They induced complete remissions in up to 85% of patients. Purine analogs are known to induce autoimmune phenomena, but there are no reports of autoimmune thrombocytopenia after treatment with pentostatin. This case report describes the very rare association of pentostatin-treated hairy cell leukemia and autoimmune thrombocytopenia. Encouraged by first reports of promising activity of the anti-CD20 monoclonal antibody rituximab in patients with autoimmune disorders, we decided to treat our patient with rituximab in the conventional dose of 375 mg/m(2) i.v. weekly for 4 cycles. One week after the first administration, the peripheral blood count has recovered with a normal platelet count. 22 weeks after completion of therapy, the patient is still in complete hematologic remission without further medication. In conclusion, rituximab seems to be a new, promising drug in the treatment of refractory autoimmune thrombocytopenia even in patients with underlying lymphoproliferative disorders.

Antibiotics, Antineoplastic↗
PubMed2003

The symmetry of initial divisions of human hematopoietic progenitors is altered only by the cellular microenvironment.

OBJECTIVE: We examined if cellular elements or adhesive ligands were able to alter asymmetric divisions of CD34(+)/CD38(-) cells in contrast to soluble factors at a single cell level. MATERIALS AND METHODS: After single cell deposition onto 96-well plates, cells were cocultured for 10 days with the stem cell supporting cell line AFT024, fibronectin (FN), or bovine serum albumin (BSA). The divisional history was monitored with time-lapse microscopy. Subsequent function for the most primitive cells was assessed using the myeloid-lymphoid-initiating cell (ML-IC) assay. Committed progenitors were measured using colony-forming cells (CFC). RESULTS: Only contact with AFT024 recruited significant numbers of CD34(+)/CD38(-) cells into cell cycle and increased asymmetric divisions. Although most ML-IC were still identified among cells that have divided fewer than 3 times, a significant number of ML-IC shifted into the fast-dividing fraction after exposure to AFT024. The increase in ML-IC frequency was predominantly due to recruitment of quiescent and slow-dividing cells from the starting population. Increase in CFC activity induced by AFT024 was found only among rapidly dividing cells. CONCLUSIONS: For the first time, we have demonstrated that asymmetric divisions can be altered upon exposure with a stem cell-supporting microenvironment. For the primitive subset of cells (ML-IC), this was predominantly due to recruitment into cell cycle and increased rounds of cycling without loss of function. Exposure to AFT024 cells also increased proliferation and asymmetric divisions of committed CFC. Hence direct communication between hematopoietic progenitors with stroma cells is required for maintaining self-renewal potential.

ADP-ribosyl Cyclase↗
PubMed2003

Disease activity and pretreatment, rather than hypogammaglobulinaemia, are major risk factors for infectious complications in patients with chronic lymphocytic leukaemia.

To identify patients at high risk of life-threatening infections, we retrospectively analysed the prevalence of infectious complications in 187 chronic lymphocytic leukaemia patients treated in our institution since 1999 and correlated them with clinical features. A questionnaire with detailed questions regarding infectious complications was mailed to patients and their general practitioners. Major infections (requiring intravenous antibiotics or inpatient treatment) were reported in 37 patients (19.8%) and minor infections (requiring oral antibiotics and outpatient treatment) in 113 patients (60.4%). Univariate analysis identified advanced disease (P = 0.02), gender (P = 0.01), duration of disease (P = 0.007), number of previous chemotherapy regimens (P < 0.001), previous therapy with purine analogues and monoclonal antibodies (P < 0.001; P = 0.019), massive splenomegaly (P = 0.03), low granulocyte count (P < 0.001), low serum immunoglobulin concentration (P = 0.005), low haemoglobin concentration (P < 0.001) and high serum lactate dehydrogenase (LDH) concentration (P < 0.001) as risk factors for major infections. In multivariable logistic regression analysis, only the number of previous chemotherapy regimens (risk ratio [RR] = 1.8; 95% confidence interval [CI] 1.2-8.0) and haemoglobin concentration (RR = 0.6; CI 0.5-0.8) remained significant for major infections. The number of previous chemotherapy regimens was the only independent risk factor for minor (RR = 7.6; CI 2.2-25.7) and varicella-zoster virus infections (RR = 2.1; CI 1.3-3.4). In untreated patients, the only risk factor for major infections was LDH concentration. Patients treated with purine analogues or autologous stem cell transplantation had a higher risk of developing viral infections. In conclusion, disease activity and pretreatment extent have a stronger impact on the risk of severe infectious complications than hypogammaglobulinaemia. Preferably, prophylactic strategies should be evaluated in patients defined by these parameters.

Adult↗
PubMed2003

Dissociation of putative graft-versus-haematopoiesis and graft-versus-myeloma effects in patients with rapidly progressive multiple myeloma.

This study evaluates the immunological effects in 21 patients with multiple myeloma (MM) following allogeneic stem cell transplantation with a non-myeloablative conditioning regimen. Patients were heavily pretreated, most of them having progressed despite one to three courses of high dose chemotherapy followed by autologous stem cell rescue. For patients conditioned with low dose total body irradiation and Fludarabine, development of full (100%) donor chimerism (FDC) within the first 3-4 months strongly depended on the number of T cells transplanted. This putative graft-versus-haematopoiesis effect, however, did not coincide with clinical response. Rather, 10 of 17 patients progressed although FDC in peripheral blood was achieved. In contrast, clinical graft-versus-host disease (GvHD) of grade III-IV was associated with disease remission. Four of six patients achieved complete remission (CR) and one patient achieved a partial remission (PR) in close temporal relation with their acute GvHD. Two of four patients in CR succumbed to the consequences of this side effect. One patient in PR progressed soon after successful treatment of the GvHD, one of two patients with a long-lasting CR developed chronic GvHD. Our observations suggest the existence of two distinct immune effects in MM following allogeneic transplantations with reduced conditioning regimen. First, the putative graft-versus-haematopoiesis effect that induced FDC was observed in all patients receiving unmanipulated grafts. Secondly, the graft-versus-myeloma effect that induced CR did not correlate with FDC but was associated with grade III-IV GvHD in our group of heavily pretreated patients.

Acute Disease↗
PubMed2003

Autologous bone marrow transplantation in adult patients with acute lymphoblastic leukemia.

Autologous bone marrow transplantation (ABMT) was introduced as a treatment for terminal leukemic relapse more than 40 years ago. For childhood acute lymphoblastic leukemia (ALL) the role of ABMT is well defined. Some studies suggest that it is also beneficial for adult patients with high-risk factors or with relapse. However, these inferences are based on a relatively small number of patients with short follow-up. Nevertheless patients with high-risk ALL are candidates for ABMT if no histocompatible sibling is available. Similarly patients in second or later complete remission (CR) in the absence of a histocompatible donor may derive benefit from ABMT. The different conditioning regimens used by the treatment centers are associated with different toxicities but none has been proven to be superior than others. In the majority of studies the marrow has been purged of leukemic cells, but this maneuver has never been evaluated in a randomized comparative trial. Transplant related mortality rate of ABMT is low compared to allogeneic transplantation. The GvL effect, which is important to eliminate malignant cells in acute and chronic myelocytic leukemia, has not been definitively demonstrated in ALL. The tyrosine-kinase inhibitor STI 571 offers new perspectives for patients with the Phl/bcr/abl translocation. It may be especially useful for treating minimal residual disease (MRD) before and/or after ABMT.

Bone Marrow Purging↗
PubMed2003

Unrelated donor transplantation after reduced intensity conditioning as an approach for patients lacking related donors for allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (SCT) after reduced intensity conditioning (RIC) provides a new curative treatment option for patients usually not eligible for allogeneic SCT. Because the majority of patients lack HLA-identical sibling donors (SD), unrelated donor (UD) transplantation is performed increasingly. In this retrospective analysis, we have reviewed our experience with reduced-intensity conditioning regimens, comparing related and unrelated donors. From November, 1997, to February, 2002, 51 patients with hematological malignancies received allogeneic SCT after various RIC regimens. A total of 31 had a related donor, and the remaining 20 had an unrelated donor (UD). Both groups were comparable with respect to age and gender. We observed a trend toward higher rate of graft failure in the unrelated donor group with 11% compared to 3% in the related donor group (p = 0.55). The rate of acute graft-versus-host disease (GVHD) II-IV was 36% in the RD group versus 44% for the UD group; severe GVHD III-IV occurred in 26% and 22%, respectively. There were more serious infections in the unrelated donor group with 25% compared to 16%. Transplant-related mortality was 13% (RD group) versus 30% (UD group). At 21 months, progression-free survival was 30% in both groups. The Kaplan Meier estimate of overall survival was 40% (RD) and 30% (UD group). In summary, we found no statistically significant difference regarding progression free and overall survival, despite a trend for more graft failure and increased transplant-related complications associated with the use of stem cells from unrelated donors.

Adult↗
PubMed2003

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.

Amyloid↗
PubMed2003

Hematopoietic stem cells: can old cells learn new tricks?

Since the establishment of cell lines derived from human embryonic stem (ES) cells, it has been speculated that out of such "raw material," we could some day produce all sorts of replacement parts for the human body. Human pluripotent stem cells can be isolated from embryonic, fetal, or adult tissues. Enormous self-renewal capacity and developmental potential are the characteristics of ES cells. Somatic stem cells, especially those derived from hematopoietic tissues, have also been reported to exhibit developmental potential heretofore not considered possible. The initial evidences for the plasticity potential of somatic stem cells were so encouraging that the opponents of ES cell research used them as arguments for restricting ES cell research. In the past months, however, critical issues have been raised challenging the validity and the interpretation of the initial data. Whereas hematopoietic stem-cell therapy has been a clinical reality for almost 40 years, there is still a long way to go in basic research before novel therapy strategies with stem cells as replacement for other organ systems can be established. Given the present status, we should keep all options open for research in ES cells and adult stem cells to appreciate the complexity of their differentiation pathways and the relative merits of various types of stem cells for regenerative medicine.

Adult↗
PubMed2002

Clinicopathologic correlations of genomic gains and losses in follicular lymphoma.

PURPOSE: To evaluate the clinical relevance of genomic aberrations in follicular lymphomas (FLs). PATIENTS AND METHODS: In this study, we analyzed 124 biopsy samples of patients with FL using comparative genomic hybridization. RESULTS: In 87 cases (70%), genomic imbalances were detectable. The most frequent aberrations were gains of chromosome arms 7p (21 patients), 7q (21 patients), Xp (16 patients), 12q (15 patients), and 18q (14 patients) as well as losses on 6q (21 patients). Grades 2 and 3 according to the World Health Organization classification correlated with a more complex karyotype (P <.0001). In a subset of 82 patients, a comprehensive clinical data set was available. In a multivariate analysis including all clinical risk factors of the International Prognostic Index as well as genomic aberrations, the loss of material on chromosomal bands 6q25q27 was the strongest predictor of a shorter survival (P =.0001; hazard ratio, 6.5), followed by elevated serum lactate dehydrogenase level (P =.0009; hazard ratio, 4.9), the presence of more than one extranodal manifestation (P =.017; hazard ratio, 4.2), and age greater than 60 years (P =.022; hazard ratio, 2.6). CONCLUSION: These data indicate that genomic aberrations may contribute significantly to risk assessment in patients with FL, the majority of whom are included in low-risk groups using established clinical prognostic scores.

Adult↗
PubMed2002

Retroviral vector integration occurs in preferred genomic targets of human bone marrow-repopulating cells.

Increasing use of hematopoietic stem cells for retroviral vector-mediated gene therapy and recent reports on insertional mutagenesis in mice and humans have created intense interest to characterize vector integrations on a genomic level. We studied retrovirally transduced human peripheral blood progenitor cells with bone marrow-repopulating ability in immune-deficient mice. By using a highly sensitive and specific ligation-mediated polymerase chain reaction (PCR) followed by sequencing of vector integration sites, we found a multitude of simultaneously active human stem cell clones 8 weeks after transplantation. Vector integrations occurred with significantly increased frequency into chromosomes 17 and 19 and into specific regions of chromosomes 6, 13, and 16, although most of the chromosomes were targeted. Preferred genomic target sites have previously only been reported for wild-type retroviruses. Our findings reveal for the first time that retroviral vector integration into human marrow-repopulating cells can be nonrandom (P =.000 37).

Animals↗
PubMed2002

Polymorphisms of the tumor necrosis factor-alpha gene promoter predict for outcome after thalidomide therapy in relapsed and refractory multiple myeloma.

Thalidomide (Thal) is a drug with antiangiogenic, anti-inflammatory, and immunomodulatory properties that was found to inhibit the production of tumor necrosis factor-alpha (TNF-alpha) in vitro. We studied single nucleotide polymorphisms at positions -308 and -238 of the TNF-alpha gene promoter and measured the corresponding TNF-alpha cytokine levels in 81 patients (pts) with refractory and relapsed multiple myeloma (MM) who were treated with Thal. In myeloma pts carrying the TNF-238A allele (n = 8), we found a correlation with higher pretreatment TNF-alpha levels in peripheral blood (P =.047). After Thal administration, this TNF-238A group had a prolonged 12-month progression-free and overall survival of 86% and 100% versus 44% and 84% (P =.003 and P =.07) in pts with the TNF-238G allele, respectively. These findings suggest that regulatory polymorphisms of the TNF-alpha gene can affect TNF-alpha production and predict the outcome after Thal therapy, particularly in those MM pts who are genetically defined as "high producers" of TNF-alpha.

Adult↗
PubMed2002

P53 is the strongest predictor of survival in high-risk primary breast cancer patients undergoing high-dose chemotherapy with autologous blood stem cell support.

Our purpose was to determine the predictive value of tumor biologic parameters in patients with HRPBC who received HDCT with ASCT as first-line treatment. From September 1992 to May 2000, 149 stage II or III HRPBC patients were enrolled in a single-arm trial using a tandem HDCT regimen followed by ASCT. Her2/neu, p53, Ki67 and bcl-2 protein expression was studied using immunohistochemic staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA index) and tumor cell proliferation (SPF) were measured by DNA flow cytometry. The relationship between these tumor biologic parameters, on the one hand, and DFS, DDFS and OS, on the other, was analyzed. With a median follow-up of 43 months (range 7-106), p53 protein accumulation (p = 0.000004), negative combined hormone receptor status (p = 0.003) and Her2/neu overexpression (p = 0.02) were significant negative predictors of OS in univariate analysis. A poorer DFS was associated with p53 positivity (p = 0.04) and nodal ratio > or = 0.8 (p = 0.008). Poorer DDFS was associated with p53 positivity (p = 0.03). In multivariate analysis, Her2/neu overexpression (RR = 3.86, 95% CI 1.48-10.1, p = 0.006) and p53 overexpression (RR = 6.06, 95% CI 2.22-16.52, p < 0.001) proved to be independent predictors of adverse OS. p53 overexpression was the only independent predictor of DFS (RR = 2.21, 95% CI 1.07-4.57, p = 0.03). p53 overexpression and Her2/neu overexpression are independent negative predictors of survival in HRPBC treated with HDCT. The adverse impact of these biologic features was probably not altered by HDCT. For HRPBC patients with tumors not overexpressing Her2/neu or p53, HDCT may be an appropriate approach to achieve long-term survival and tumor control.

Adult↗
PubMed2002

Centrosome aberrations in acute myeloid leukemia are correlated with cytogenetic risk profile.

Genetic instability is a common feature in acute myeloid leukemia (AML). Centrosome aberrations have been described as a possible cause of aneuploidy in many human tumors. To investigate whether centrosome aberrations correlate with cytogenetic findings in AML, we examined a set of 51 AML samples by using a centrosome-specific antibody to pericentrin. All 51 AML samples analyzed displayed numerical and structural centrosome aberrations (36.0% +/- 16.6%) as compared with peripheral blood mononuclear cells from 21 healthy volunteers (5.2% +/- 2.0%; P <.0001). In comparison to AML samples with normal chromosome count, the extent of numerical and structural centrosome aberrations was higher in samples with numerical chromosome changes (50.5% +/- 14.2% versus 34.3% +/- 12.2%; P <.0001). When the frequency of centrosome aberrations was analyzed within cytogenetically defined risk groups, we found a correlation of the extent of centrosome abnormalities to all 3 risk groups (P =.0015), defined as favorable (22.5% +/- 7.3%), intermediate (35.3% +/- 13.1%), and adverse (50.3% +/- 15.6%). These results indicate that centrosome defects may contribute to the acquisition of chromosome aberrations and thereby to the prognosis in AML.

Acute Disease↗
PubMed2002

Catheter-related infection and thrombosis of the internal jugular vein in hematologic-oncologic patients undergoing chemotherapy: a prospective comparison of silver-coated and uncoated catheters.

BACKGROUND: Catheter-related venous thrombosis is one of the most frequent complications of central venous catheters (CVCs). This complication occurs in 4- 40% of patients with hematologic malignancies receiving conventional chemotherapy after placement of CVCs. METHODS: The objective of this prospective study was to assess whether a silver-coated CVC poses an additional risk in the development of catheter-related thrombosis in hematologic-oncologic patients. Patients were randomized to receive either silver-coated polyurethane catheters (BactiGuard; Metacot, Stockholm, Sweden) or uncoated standard polyurethane catheters (Cavatheter, Fresenius AG, Bad Homburg, Germany) for central venous access. Silver-coated catheters (n = 120) and standard catheters (n = 113) were inserted into the jugular vein in 233 consecutive patients. Variables that may be significant for the development of thrombosis were comparable in the two groups. After removal of the CVC, the patency of both jugularian veins internal as well as external was assessed with real-time ultrasound (Sonolayer-SAL-35A; Toshiba, Tokyo, Japan). RESULTS: Four of 233 patients (1.5%) were found to have venous thrombosis. Incomplete occlusion of the internal jugular vein occurred in 2 patients (0.75%, parietal thrombosis), and complete thrombosis, although clinically silent, was found in 2 patients (0.75%). There was no difference between patients with silver-coated and uncoated CVCs. CONCLUSIONS: The authors concluded that this novel silver-coated CVC does not cause a higher rate of central venous thrombosis compared with standard CVCs. The low overall incidence of central venous thrombosis might be attributed to the routine application of low-dose heparin in our patients during chemotherapeutic treatment.

Antineoplastic Agents↗
PubMed2002

Functional analysis of initial cell divisions defines the subsequent fate of individual human CD34(+)CD38(-) cells.

OBJECTIVE: We assessed the relationship of individual cell divisional behavior with the functional fate of stem cell candidates at the single cell level. MATERIALS AND METHODS: Individual CD34(+)CD38(-) cells derived from cord blood (88-352 cells in each of 25 experiments) were cultured in early-acting conditioned medium (EACM) or late-acting proliferation medium (LAPM). The initial cell divisions were microscopically monitored every 12 to 24 hours and then assessed for primitive function in the myeloid lymphoid-initiating cell assay and committed function in the colony-forming cell (CFC) assay. RESULTS: Despite a higher proliferative capacity in LAPM, significantly more quiescent cells (11.1 +/- 1.7%) were found in LAPM than in EACM cultures (1.1 +/- 0.4%; p < 0.001). No differences were observed in the initially plated CD34(+)Cd38(-) cells that produced asymmetrically dividing progeny. The majority of cells with subsequent ML-IC function divided in EACM but were found among quiescent cells in LAPM conditions. All cycling cells with subsequent ML-IC capacity initially remained quiescent for at least 96 hours. All ML-IC had been recruited exclusively (100%) from either cytokine nonresponsive (quiescent) or slow and asymmetrically dividing cells (1-2 divisions). In contrast, the majority of CFCs entered the cell cycle immediately after plating, have divided more than two times, and only 20.2 +/- 5.5% of the cycled CFC divided asymmetrically. CONCLUSIONS: Asymmetric divisional behavior of CD34(+)CD38(-)cells cannot be influenced by culture conditions. Primitive ML-IC can be distinguished from committed CFC by initial quiescence or asymmetric divisions. Committed CFC cycle rapidly and symmetrically.

ADP-ribosyl Cyclase↗
PubMed2002

Level of CD 20-expression and efficacy of rituximab treatment in patients with resistant or relapsing B-cell prolymphocytic leukemia and B-cell chronic lymphocytic leukemia.

Rituximab (IDEC C2B8) is a chimeric human-mouse monoclonal anti-CD20 antibody that has been proven to be effective for the treatment of patients with CD20 positive leukemia and lymphoma. The level of CD20-expression in patients with B-cell chronic lymphocytic leukemia (B-CLL) is low in comparison to other B-cell lymphomas and normal B-cells. Previous experience with rituximab treatment in small series of patients with B-CLL suggest that it is less effective in B-CLL than in follicular lymphomas. We analyzed the correlation between CD20-expression level and efficacy of rituximab treatment in eight patients with refractory or relapsed B-CLL and two patients with B-cell prolymphocytic leukemia (B-PLL). We could not identify any correlation between CD20-expression and efficacy of rituximab treatment.

Aged↗
PubMed2002

Stem cell dose and tumorbiologic parameters as prognostic markers for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous blood stem cell support.

We report on the prognostic significance of tumorbiologic parameters and CD34(+) cell dose in 120 patients with metastatic breast cancer (MBC) who received high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation as first-line treatment. Her2/neu, p53, Ki67, and bcl-2 protein expression were studied using immunohistochemical staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA-index) and tumor cell proliferation (S-phase fraction) were measured by DNA flow cytometry. The relationship between these parameters and the CD34(+) cell dose and progression free (PFS) and overall survival (OS) was analyzed. With a median follow-up period of 40 months (range, 7-89 months), no more than two metastatic sites (relative risk [RR] = 3.84 [95% confidence interval (CI) 1.49-10]; p =.005) and hyperploidy (RR = 2.58 [95% CI 1.26-5.26]; p =.009) were independent predictors of longer PFS according to multivariate analysis. Independent prognostic factors of longer OS included one or two metastatic sites (RR = 4.16 [95% CI 1.96-4.16]; p <.001), a positive combined hormone receptor status (RR = 2.45 [95% CI 1.45-4.14]; p =.001) and a high number of infused stem cells (>7.8 x 10(6) CD34(+) cells per kg body weight) (RR = 2.0 [95% CI 1.17-3.42]; p =.01). In conclusion, positive hormone receptors, < or =2 metastatic sites, high DNA-index and high CD34(+) cell dose (>7.8 x 10(6) CD34(+) cells per kg) are predictors for a favorable outcome after autotransplantation for MBC. Our observation might indicate a favorable effect of HDCT in MBC patients with overexpression of Her2/neu who might have a worse prognosis when treated with conventional chemotherapy.

Adult↗