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Jerald P Radich

Publications and source records attributed to Jerald P Radich.

43 records · Page 3Linked to original sources
PubMed2003

Progenitor cell involvement is predictive of response to induction chemotherapy in paediatric acute myeloid leukaemia.

In acute myeloid leukaemia (AML), involvement of early progenitor cells may predict poor response to induction chemotherapy. We evaluated the involvement of early progenitor cells in two AML subtypes with a favourable prognosis [t(8;21) and t(15;17)], and a subtype with poor prognosis (monosomy 7). CD34+CD33- cells were isolated by fluorescence-activated cell sorting, grown in liquid medium followed by culture in semi-solid medium, and the colonies that were formed were analysed for the identifiable genetic markers. Two of 136 colonies from six t(8;21) AML patients expressed the AML1-ETO transcript, and all six patients achieved remission after induction. None of 192 colonies from five t(15;17) AML patients expressed the RARalpha-PML transcript and all achieved remission. In contrast, in three of 10 cases of monosomy 7 AML, colonies were positive for monosomy 7, and all three patients failed to enter remission. However, five of six evaluable patients with colonies negative for monosomy 7 entered remission. These data support the hypothesis that leukaemic involvement of early progenitor cells affects the response to induction chemotherapy.

Acute Disease↗
PubMed2003

Predictors of relapse and overall survival in Philadelphia chromosome-positive acute lymphoblastic leukemia after transplantation.

Allogeneic transplantation offers a potential cure for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). We performed a retrospective analysis examining pretransplantation and posttransplantation prognostic factors in 90 patients with Ph+ ALL. The median age of the patients was 33 years, with slightly more than half of the patients (58%) in clinical remission at the time of transplantation. Overall, patients had a nonrelapse mortality rate of 30%, a relapse percentage of 34%, and an estimated 5-year disease-free survival rate of 30%. Pretransplantation risk factors for relapse included the expression of the p190 transcript (relative risk [RR] = 5.1; P =.037), evidence of morphologic disease at the time of transplantation (RR = 3.9; P <.001), and type of donor (RR = 2.5; P =.015), with patients receiving autologous or matched related transplants having the highest risk of relapse. The detection of minimal residual disease by reverse transcription polymerase chain reaction for bcr-abl transcripts was a significant posttransplantation risk factor for relapse (RR = 4.4; P =.001), with posttransplantation patients expressing the p190 transcript having the highest risk of relapse (RR = 8.7; P =.0001). In addition, patients with chronic extensive graft-versus-host disease showed a significantly lower risk of relapse (RR = 0.33; P =.038). Thus, these findings indicate that several pretransplantation and posttransplantation risk factors exist for patients with Ph+ ALL. Together, these factors can be used to improve our risk stratification of patients with Ph+ ALL who undergo transplantation, which will greatly enhance our ability to counsel these patients and potentially lead to the development of more specific treatment plans for them.

Adolescent↗
PubMed2002

Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome.

A total of 109 patients (aged 6-66 years; median, 46 years) with myelodysplastic syndrome (MDS) were treated with busulfan (BU) targeted to plasma concentrations of 800 to 900 ng/mL plus cyclophosphamide (CY), 2 x 60 mg/kg, and hemopoietic stem cell (HSC) transplantation from related (n = 45) or unrelated donors (n = 64). At the time of transplantation, 69 patients had less than 5% myeloblasts in the marrow, and 40 patients had more advanced disease. All but 2 evaluable patients had engraftment. The Kaplan-Meier estimates of 3-year relapse-free survival (RFS) were 56% for related and 59% for unrelated recipients. The cumulative incidences of relapse were 16% for related and 11% for unrelated recipients. Nonrelapse mortality (NRM) at 100 days (3 years) was 12% (28%) for related and 13% (30%) for unrelated recipients. The only factor significant for RFS was the etiology of MDS (de novo better than treatment related; P =.03). Factors significantly correlated with relapse were advanced French-American-British classification (P =.002) and International Prognostic Scoring System score (P =.009), poor-risk cytogenetics (P =.03), and treatment-related etiology (P =.03). None of the factors examined was statistically significant for NRM. Patient age and donor type had no significant impact on outcome. RFS tended to be superior in patients receiving transplants with peripheral blood rather than marrow stem cells. Thus, a targeted BUCY regimen provided effective transplant conditioning for patients with MDS receiving transplants from HLA-identical siblings or alternative donors. Although there was still considerable nonrelapse morbidity and mortality, the present regimen was used successfully even in patients older than 60 years of age.

Adolescent↗
PubMed2002

Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases.

Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in multi-center study to investigate the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradi ation (TBI)-based regimen. A total of 192 patients (median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age 53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n = 48; marrow graft, n = 15). Diagnoses included multiple myeloma (n = 61), myelodysplastic syndrome (n = 55), chronic myeloid leukemia (n = 31), non-Hodgkin lymphoma (n = 31), acute myeloid leukemia (n = 28), chronic lymphocytic leukemia (n = 24), Hodgkin Disease (n = 14). The conditioning regimen was fludarabine 30 mg/m2/d x 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression was combined mycophenolate mofetil an cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100-1,188) days. Nonfatal graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33% grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive. The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projecte 2-year survival and progression-free survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100-468) days. Graft rejection occurred in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred in 50% of patients. Of the 63 URD HSCT patients, 54% were alive, 37% in CR, 3% PR, and 14% with disease progression or relapse. Related and unrelated nonmyeloablative HSCT is feasible and potentially curative in patients with advanced hematological malignancies who have no other treatment options.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Molecular measurement of minimal residual disease in Philadelphia-positive acute lymphoblastic leukaemia.

The Philadelphia chromosome (Ph) is found in approximately 5-25% of acute lymphoblastic leukaemia (ALL) cases and is the harbinger of a poor outcome. Polymerase chain reaction (PCR) assays can detect leukaemia-specific genetic lesions down to a sensitivity approaching one leukaemia cell in a background of a million normal cells. In Ph(+) ALL, the unique BCR-ABL translocation is thus a specific target for the detection of minimal residual disease (MRD). After chemotherapy or transplantation the detection of residual BCR-ABL transcripts is associated with a high risk of subsequent relapse. With the advent of novel therapeutics that target the structure and function of BCR-ABL, the detection of MRD may allow for targeted therapy that could abort a potential relapse.

Animals↗
PubMed2002

Curative therapy of advanced essential thrombocythemia or polycythemia vera by hemopoietic stem cell transplantation.

Twenty-five patients with advanced essential thrombocythemia (ET; n = 13) or polycythemia vera (PV; n = 12) received hemopoietic stem cell transplants (HSCT) at the Fred Hutchinson Cancer Research Center. In most cases the indication to perform an HSCT was myelofibrosis with splenomegaly and peripheral blood cytopenias or the development of a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients were 18-60 (median 43) years old with intervals from diagnosis to HSCT of 8-348 (median 168) months. All but five patients had been treated with cytotoxic agents, and nine patients were splenectomized before transplant. Conditioning was performed with chemotherapy only or chemotherapy plus total body irradiation regimens followed by the infusion of either marrow (n = 19) or peripheral blood stem cells (n = 6) from related (n = 16) or unrelated (n = 9) donors. All evaluable patients showed sustained neutrophil engraftment. Nine patients (seven with AML/MDS, two with myelofibrosis) died of transplant-related complications, and 16 are surviving, 14 of them in continuous unmaintained remission. With a median follow-up of 41 (range 5-116) months after transplant, survival at 3 years is 64%. These data provide evidence that HSCT can be a curative treatment for patients with advanced PV and ET.

Adolescent↗