Biomedical subjects

M G Chen

Publications and source records attributed to M G Chen.

At least 19 recordsLinked to original sources

PubMed2003

Lymphocyte recovery after allogeneic bone marrow transplantation predicts risk of relapse in acute lymphoblastic leukemia.

Allogeneic blood and marrow transplantation (BMT) is curative for many patients with high-risk and relapsed acute lymphoblastic leukemia (ALL). However, relapse is an important cause of post-transplantation failure, and there are no reliable markers to predict relapse. A retrospective review of patients with ALL who underwent matched related allogeneic BMT was carried out to examine whether the rate of lymphocyte recovery after transplantation had any prognostic value in ALL. The absolute lymphocyte count (ALC) at days 21 and 30 after transplantation was obtained for 43 patients who received transplants during an 18-year period. Patients with an ALC of 175 x 10(6)/l or less on day 21 were more likely to relapse than those with ALC greater than 175 x 10(6)/l (relative risk, 4; 95% confidence interval, 1.5-11.2). Patients with slower lymphocyte recovery had significantly lower relapse-free survival than those with faster recovery (P=0.0028). There was also a trend toward poorer overall survival among those with a slow lymphocyte recovery (log-rank test; P=0.028). The rate of lymphocyte recovery is prognostic in patients with ALL undergoing allogeneic BMT, and this should be integrated with other predictors to identify patients at high risk of relapse. Such patients could be considered for interventions aimed at prevention of relapse, including rapid withdrawal of immunosuppressive medication or donor lymphocyte infusion.

Adolescent↗

PubMed2002

Omission of day +11 methotrexate after allogeneic bone marrow transplantation is associated with increased risk of severe acute graft-versus-host disease.

The combination of CYA and short-course MTX is commonly used for GVHD prophylaxis after allogeneic BMT. Severe mucositis and organ dysfunction early after transplantation often lead to omission of the day +11 dose of MTX. To examine whether this omission increases the risk of acute or chronic GVHD, we reviewed 135 allogeneic BMTs performed at our institution in which CYA and short-course MTX prophylaxis were used. Patients receiving less than three doses of MTX and those who died before day +11 were excluded. Of the 123 eligible patients, 84 received all four doses and 39 received three doses, with the fourth dose withheld because of severe mucositis (n = 27) or hepatic or renal dysfunction (n = 12). Acute GVHD of any grade developed in 23 patients (59%) in the three-dose group compared with 57 patients (68%) in the four-dose group (P = 0.33). Chronic GVHD developed in 15 patients (38%) in the three-dose group compared with 31 patients (37%) in the four-dose group (P = 0.87). There was no difference in the overall rate of acute or chronic GVHD between the groups. However, the three-dose group was more likely to develop grade III or IV acute GVHD (12 of 39 (31%) ) compared with the four-dose group (12 of 84 (14%); P = 0.03). Relapse-free survival was similar for the two groups. We conclude that omitting day +11 MTX appears to increase the risk of severe acute GVHD.

Acute Disease↗

PubMed2001

Radiation therapy for symptomatic hepatomegaly in myelofibrosis with myeloid metaplasia.

OBJECTIVE: To describe the experience with liver irradiation in advanced cases of myelofibrosis with myeloid metaplasia (MMM). METHODS: Over a 20-yr period, 14 patients with MMM were treated with a total of 25 courses of liver, abdominal, or abdominal and pelvic irradiation for symptomatic hepatomegaly with (5 patients) or without (9 patients) ascites. All 14 patients had advanced disease and 11 (79%) had previous splenectomy. The median radiation therapy (RT) dose per course was 150 cGy (range 50-1000) administered at a median of six fractions. Four patients received two to six courses. RESULTS: Twelve of the 14 patients (86%) had a transient (median 3 months) subjective response from RT. However, in only 35% of these was there a transient (median 3 months) decrease in palpable liver size. Four of the five patients with ascites experienced a short-term response from RT. Eight of the 13 patients suitable for evaluation (62%) had treatment-associated cytopenia, often in the form of anemia and/or thrombocytopenia. At last follow-up, 10 patients (71%) had died after a median of 7 months (range 0.1-23) and 4 were alive at 3, 20, 33, and 57 months after RT. CONCLUSIONS: Low-dose abdominal RT for symptomatic hepatomegaly or ascites associated with advanced-stage MMM is myelosuppressive and provides only temporary and mainly subjective and short-lived relief.

Abdomen↗

PubMed2001

Prophylaxis of graft-versus-host disease with cyclosporine-prednisone is associated with increased risk of chronic graft-versus-host disease.

To determine the effect of two different graft-versus-host disease (GVHD) prophylactic regimens--cyclosporine with short course of methotrexate (CYA-MTX) and cyclosporine with prednisone (CYA-PRED)--on the incidence of chronic GVHD (cGVHD), we retrospectively reviewed the outcomes of 196 consecutive allogeneic related blood and marrow transplants performed at our institution utilizing one of these regimens. CYA-PRED was given to patients who were transplanted more recently because of concern about the increased risk of veno-occlusive disease of the liver, increased mucositis, and slower engraftment in patients receiving CYA-MTX. Prophylaxis with CYA-PRED was associated with a higher risk of development of cGVHD (risk ratio (RR) 3.5; 95% confidence intrerval (CI), 2.2-5.4). The proportion of patients with extensive disease among those developing cGVHD was higher in the CYA-PRED group (71%) than in the CYA-MTX group (57%), although this difference was not statistically significant. The cumulative probability of extensive cGVHD at 2 years was higher in the CYA-PRED group (RR 4.2, 95% CI, 2.4-7.4). Development of acute GVHD and cytomegalovirus mismatch were independent predictors of increased risk of cGVHD. We conclude that GVHD prophylaxis with CYA-PRED is associated with a higher overall rate of cGVHD compared to CYA-MTX. The type of GVHD prophylaxis should be considered when comparing the incidence of cGVHD reported in different studies.

Adolescent↗

PubMed2001

Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia.

Allogeneic BMT is potentially curative for patients with acute myelogenous leukemia (AML) in first remission. However, many patients relapse after transplantation. Various immunotherapeutic options have been attempted with variable success in preventing relapse. Early identification of patients at high risk for relapse could allow prompt intervention. We examined the effect of slow lymphocyte recovery after sibling-matched allogeneic BMT on the risk of relapse in patients with AML. We also examined the effect of prednisone-containing GVHD prophylaxis on the rate of lymphocyte recovery. Patients with absolute lymphocyte count (ALC) <150 x 10(6)/l by day +30 had a 3.5-fold higher risk of relapse (P = 0.0088) and a lower overall survival (P = 0.0079) than patients with a higher ALC. We did not find correlation between lymphocyte count determined earlier in the post-transplantation course (day +21) and the risk of relapse. Patients receiving prednisone had a significantly lower ALC at day +30 than those who did not receive prednisone (289 vs 549 x 10(6)/l, P = 0.002). We conclude that a slow lymphocyte recovery after allogeneic BMT for AML is strongly predictive of subsequent relapse and that the type of GVHD prophylaxis should be considered when analyzing lymphocyte recovery.

Adolescent↗

PubMed2001

Possible origin of extrachromosomal DNA from human lymphocytes following in vitro treatment by phytohemagglutinin.

Lymphocytes respond to chemical or pathological challenges by synthesizing episomes or extrachromosomal DNA (eDNA). Phytohemagglutinin (PHA) is a mitogen for T lymphocytes and can stimulate the increased production of episomes as well as the release of eDNA, interleukin-2, and other factors. However, the origin of this eDNA is largely unknown. To confirm the observation on the localization of an antibody directed against a 23-kb segment of bull acrosomal DNA in cultured human lymphocytes, we performed analyses by fluorescence in situ hybridization (FISH) using the same DNA as a molecular probe.

Cells, Cultured↗

PubMed2000

Delayed stem cell transplantation for the management of relapsed or refractory multiple myeloma.

The optimal timing of stem cell transplantation for multiple myeloma is controversial. Late stem cell collection is undesirable because of the inability to mobilize stem cells. We report on 64 recipients of stem cells collected within 1 year after diagnosis, none of whom had transplantation in plateau phase of their disease. Patients seen within 12 months after diagnosis received four cycles of standard vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy and then had stem cells mobilized. Patients were then placed on maintenance vincristine, BCNU, melphalan, cyclophosphamide, and prednisone or melphalan and prednisone chemotherapy for 12 cycles. At the sign of first progression, transplantation occurred. Fourteen patients were refractory to VAD chemotherapy, 20 relapsed on maintenance chemotherapy, and 30 relapsed off chemotherapy. The time to platelet engraftment was not affected by the duration of stem cell cryopreservation or extent of chemotherapy exposure after mobilization. The complete response rate was 34%. The actuarial median survival from initial diagnosis, from transplant day 0, and post-transplant progression-free survival was 51, 20 and 11.4 months, respectively. The patient status at transplantation and percentage of plasma cells circulating in the blood at apheresis influenced post-transplant survival; circulating plasma cells, status at transplantation and plasma cell labeling index influenced progression-free survival. Response duration was shorter in patients relapsing on chemotherapy.

Adult↗

PubMed2000

Blood stem cell transplantation as therapy for primary systemic amyloidosis (AL).

This study investigated the response rate and toxicity of blood cell transplantation as treatment for primary amyloidosis (AL). Twenty-three patients had stem cells collected between November 1995 and September 1998. Conditioning included melphalan and total body irradiation in 16 and melphalan alone in 4. Three patients did not undergo stem cell infusion because of poor performance status. Two died of progressive amyloid at 1 and 3 months. One patient is alive on hemodialysis. Fourteen males and six females (median age, 57 years) underwent transplantation. Renal, cardiac (by echocardiography), peripheral neuropathy or liver amyloidosis occurred in 14, 12, 3, and 1, respectively. Echocardiography demonstrated an interventricular septal thickness > or = 15 mm in six patients, five of whom died post transplantation. Three patients died of progressive amyloidosis at 7, 7, and 21 months. Thirteen patients are alive with a follow-up of 3 to 26 months. Twelve (60%) fulfilled the criteria of a hematologic or organ response. Severe gastrointestinal tract toxicity was seen in five (25%). We conclude that blood cell transplantation for amyloidosis had a much higher morbidity and mortality compared with transplantation for myeloma. The best results appear to occur in patients with nephrotic syndrome as the only manifestation of their disease.

Adult↗

PubMed2000

Gene sequencing for identification of Paragonimus eggs from a human case.

OBJECTIVE: To identify the etiologic agent from a paragonimiasis patient using molecular techniques. METHODS: The complete nuclear ribosomal DNA second internal transcribed spacer (ITS2) gene sequence of eggs in sputum from a paragonimiasis patient was obtained by directly auto-sequencing its PCR product. ITS2 genes from eggs of Paragonimus westermani and Pagumogonimus skrjabini (both from animal hosts) were also sequenced for comparison. In addition, morphological comparisons were made with the eggs of the two species. RESULTS: The ITS2 gene from the human case was 100% identical with the sequence from the eggs of P. westermani from an experimentally infected dog but only 92% identical with the sequence from the eggs of P. skrjabini. Morphologically, the eggs from the human case more resembled those from P. westermani infected dog. CONCLUSION: The patient was diagnosed to be suffered from paragonimiasis westermani by gene sequence analysis.

Animals↗

PubMed1999

Early harvest and late transplantation as an effective therapeutic strategy in multiple myeloma.

Transplantation after high-dose chemotherapy prolongs survival in patients with multiple myeloma compared with standard therapy. It is unclear whether the optimal timing of transplantation is immediately after induction chemotherapy or whether stem cells may be cryopreserved for transplantation at subsequent progression or relapse. In this study, stem cells were collected within 6 months of diagnosis, followed by transplantation only at progression of myeloma. One hundred and eighteen patients with multiple myeloma had stem cells collected and cryopreserved. Eleven had transplants early in the disease after they demonstrated failure to respond to primary therapy. The remaining 107 were eligible for transplants when there was evidence of progressive disease. Of the 118 patients, 67 had transplants, nine died of progressive disease before transplantation, and 42 remain alive in plateau phase. The median survival of the group is 58.5 months; 67 are alive. Serum beta2-microglobulin, bone marrow labeling index (S phase), and hemoglobin level predicted overall survival (P < 0.006, P < 0.001, and P < 0.01, respectively). We conclude that early cryopreservation of blood stem cells followed by transplantation at progression is a feasible approach to therapy in patients with myeloma. The underlying biology of the disease has a greater impact on survival than the timing of transplantation. A prospective randomized trial is required to answer definitively the question of the optimal timing of blood cell transplantation.

Adult↗

PubMed1999

A molecular perspective on the genera Paragonimus Braun, Euparagonimus Chen and Pagumogonimus Chen.

The status of the genera Euparagonimus Chen, 1963 and Pagumogonimus Chen, 1963 relative to Paragonimus Braun, 1899 was investigated using DNA sequences from the mitochondrial cytochrome c oxidase subunit I (CO1) gene (partial) and the nuclear ribosomal DNA second internal transcribed spacer (ITS2). In the phylogenetic trees constructed, the genus Pagumogonimus is clearly not monophyletic and therefore not a natural taxon. Indeed, the type species of Pagumogonimus, P. skrjabini from China, is very closely related to Paragonimus miyazakii from Japan. The status of Euparagonimus is less obvious. Euparagonimus cenocopiosus lies distant from other lungflukes included in the analysis. It can be placed as sister to Paragonimus in some analyses and falls within the genus in others. A recently published morphological study placed E. cenocopiosus within the genus Paragonimus and probably this is where it should remain.

Animals↗

PubMed1998

Soft tissue chondroma of the parapharyngeal space: a case report.

Benign chondroma affecting the soft tissues is uncommon. This tumour is particularly rare in the neck. We present the first case of soft tissue chondroma arising in the parapharyngeal space of a 20-year-old man with a two-year history of a gradual sensation of a swelling in the pharynx with increasing snoring. The CT and pathological features of this lesion will be discussed. We suggest that a peroral approach should be considered for benign parapharyngeal tumour which has been demonstrated on imaging to be in the anterior parapharyngeal space, especially for tumours that are medial to the pterygoid muscles even though the tumour is a large one.

Adult↗

PubMed1998

Late-onset noninfectious pulmonary complications after allogeneic bone marrow transplantation.

We examined the incidence and clinical outcome of late-onset noninfectious pulmonary complications (LONIPC) in a series of 234 patients who underwent allogeneic bone marrow transplantation at our institution between April 1982 and October 1996. The 179 patients who survived 3 months or more were evaluated. Clinical, radiologic, pulmonary function, and pathologic tests were reviewed to identify 18 patients (10%) who fulfilled the diagnostic criteria of LONIPC. Accordingly, the pulmonary processes included bronchiolitis obliterans (BO, five patients), bronchiolitis obliterans with organizing pneumonia (BOOP, three patients), diffuse alveolar damage (DAD, one patient), lymphocytic interstitial pneumonia (LIP, one patient), and nonclassifiable interstitial pneumonia (NCIP, eight patients). Various methods of enhanced immunosuppressive therapy resulted in marked durable remission in nine patients (50%) (3/3 with BOOP, 3/8 with NCIP, 1/1 with DAD, 1/1 with LIP, 1/5 with BO). The presence of chronic graft-versus-host disease (cGVHD) and prophylaxis for GVHD with cyclosporine and prednisone were the only variables significantly associated with the development of LONIPC (P = 0.0001 and 0.008, respectively). Regardless of histology, a reduction in the forced expiratory volume to < 45% of the predicted range was associated with poor response to treatment. These findings suggest a strong association between cGVHD and LONIPC and that the risk of LONIPC development may be influenced by the particular method of GVHD prophylaxis. Most patients with BOOP or mild airflow limitation at diagnosis achieved durable remissions.

Adolescent↗

PubMed1998

Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia.

Twenty-three patients who had myelofibrosis with myeloid metaplasia (MMM) were treated at our institution with 50 courses of splenic irradiation (SI) for symptomatic splenomegaly. The median dose of radiation per course was 277.5 cGy, administered in a median of 7.5 fractions. 8/23 patients received multiple courses of SI. Of 49 evaluable courses of SI, 46 (93.9%) resulted in an objective decrease in spleen size. The median duration of response was 6 months (range 1-41). Reduction in spleen size was associated with symptomatic relief in all patients. Overall median survival after SI was 22 months. Significant cytopenia occurred in 10 (43.5%) patients, or 16 (32%) of the 50 courses of SI. Prolonged, life-threatening pancytopenia after a single course of SI occurred in six patients (26%), resulting in fatal sepsis or haemorrhage in three (13%). Nine patients underwent subsequent splenectomy: the perioperative mortality rate was 11%. One third of patients experienced postoperative intra-abdominal haemorrhage necessitating surgical re-exploration. SI can provide symptomatic relief and a reduction in spleen size in most MMM patients. The increased risk of postoperative bleeding in patients requiring subsequent splenectomy dictates against considering SI as an alternative to splenectomy for patients who are otherwise good surgical candidates.

Adult↗

PubMed1997

Factors influencing platelet recovery after blood cell transplantation in multiple myeloma.

We sought to determine factors that impact on the recovery of platelets after blood cell transplantation in patients with multiple myeloma. We performed retrospective analyses in 51 patients undergoing blood cell transplantation for multiple myeloma. The proportional-hazards model was applied to determine significant risk factors. Of 51 transplants, 14 patients failed to achieve a platelet count of 50 x 10(9)/l. Median time to a neutrophil count of 0.5 x 10(9)/l was 10.5 days. Median time to achieve a platelet count of 50 x 10(9)/l was 32 days. Multivariate analysis revealed that cyclophosphamide and G-CSF priming before collection of hematopoietic precursors (P < 0.001) was a positive predictor of rapid engraftment and prior exposure to melphalan given orally (P = 0.02) was a negative predictor of subsequent platelet engraftment. The number of mononuclear cells collected, the patient's disease status at the time of transplant and the presence of circulating plasma cells in the harvested product did not have a significant impact on time to platelet engraftment. We conclude that cyclophosphamide and G-CSF priming shortened the time to achieve platelet engraftment compared with G-CSF alone. Prior exposure to melphalan delayed platelet engraftment and can lead to complete failure of platelet recovery. Stem cells should be collected before melphalan administration in patients with multiple myeloma who are candidates for possible blood cell transplantation.

Adult↗

PubMed1997

Primary laryngeal lymphoma.

Primary laryngeal lymphoma is a very rare entity, with fewer than 50 cases reported in the English literature in the past 60 years. Close scrutiny of some of these case reports reveals that the larynx was not always the only site of involvement, thereby diminishing the total number of patients with primary laryngeal lymphoma to fewer than 35. The authors report a series of six patients, who were seen and evaluated at the Mayo Clinic between 1952 and 1995, with stage IAE non-Hodgkin's lymphoma of the larynx. Three patients had large-cell lymphomas according to the REAL (Revised European-American Lymphoid) classification. The other three had a small lymphocytic lymphoma, follicular small cleaved lymphoma, and follicular mixed lymphoma. All patients received radiation therapy alone as initial therapy for their disease and all patients had a complete remission to initial therapy. Four patients subsequently relapsed and the histology at relapse was the same as the initial histology in all four patients. Five patients have died, three of lymphoma, with a median survival of 67 months (range, 40 to 228 months). In view of the heterogeneity of histologies in this group of lymphomas, the variability in duration of response, and the significant number of patients who died of their disease, it is more likely that primary laryngeal lymphoma is an unusual presentation of non-Hodgkin's lymphoma than a separate disease entity. Despite the small number of patients in this study, the data would suggest that patients are best treated according to the histology of the lymphoma, rather than the limited stage and location of the disease.

Adult↗

PubMed1997

Predictive capacity of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma.

PURPOSE: The International Prognostic Factor Index has been shown to predict the outcome of patients with predominantly B-cell lymphomas classified using traditional classifications, including the Working Formulation, but its prognostic importance has not been tested in a cohort of patients with exclusively T-cell lymphomas. This study was conducted to evaluate the prognostic significance of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Seventy-eight patients (48 men and 30 women) with PTCL seen at a single institution between 1985 and 1995 were included in the analysis. The morphology and immunocytochemistry of all the original biopsy specimens were reviewed by a single pathologist and classified using the Revised European-American Lymphoma (REAL) classification. The International Prognostic Factor Index, as well as clinical and biochemical parameters, were evaluated by univariate and multivariate analyses to determine their association with patient outcome. RESULTS: The International Prognostic Factor Index strongly predicted survival when all patients were included in the analysis (P < .001). For patients < or = 60 years, the age-adjusted International Index significantly predicted long-term survival (P = .0218). For patients older than 60 years, the age-adjusted International Index also significantly predicted survival (P = .002). Liver involvement (P = .006) and bone marrow involvement (P = .014) were also significant prognostic factors in the univariate analysis, but only the International Index remained significant in the multivariate analysis (P = .001). CONCLUSION: The International Prognostic Factor Index, which significantly predicts outcome in patients with aggressive/intermediate-grade B-cell lymphomas, has similar prognostic importance in patients with PTCL.

Adolescent↗

PubMed1996

Lymphoma in soft tissue: a clinicopathologic study of 19 cases.

The authors retrospectively reviewed 19 patients who presented with lymphoma as soft tissue masses, without evidence of lymph node or skin involvement. Sites of involvement included lower extremity (seven), upper extremity (six), chest wall (three), gluteal region (two), and frontal subgaleal region (one). Histological and immunophenotypic studies revealed 12 large cell lymphomas (11 B cell and one T cell), two small noncleaved cell lymphomas (B-cell phenotype), and five low grade B-cell lymphomas (two small lymphocytic and three follicular mixed lymphomas). Patients with large cell lymphoma, including seven patients with stages I and II and five patients with stage IV, were treated with anthracycline-based chemotherapy, with or without radiation therapy. One half of these patients are dead of disease, including four of seven with low stage disease. The two patients with small noncleaved cell lymphoma had stage IE disease and were treated with chemotherapy; one died at 11 months, and the other is alive and disease free at 65 months. Patients with low grade B-cell lymphoma included four stage IE patients who were treated with radiation and one stage IV patient treated with chemotherapy. Two patients are alive and disease free, and three are dead of unrelated causes. The authors conclude that malignant lymphomas initially diagnosed in soft tissues are most commonly large cell lymphomas with a B-cell phenotype.

Adult↗