p38 mitogen-activated protein kinase has different degrees of activation in myeloproliferative disorders and myelodysplastic syndromes.

The goal of the present study was to evaluate the activation patterns of p38 mitogen-activated protein kinase (MAPK) in myeloproliferative disorders (MPDs) and myelodysplastic syndromes (MDSs). Phosphorylated (activated) p38 MAPK was analyzed immunohistochemically in formalin-fixed decalcified bone marrow core biopsy specimens from 32 MPD, 33 MDS, and 11 control cases. Moderate p38 activation was commonly seen in MDS, whereas weak p38 activation was seen in all MPD cases and all control cases but 1 in the erythroid lineage.

Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences.

A new hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was effective in predicting outcomes among patients with hematologic malignancies who underwent HCT at Fred Hutchinson Cancer Research Center (FHCRC). Here, we compared the performance of the HCT-CI to 2 other indices and then tested its capacity to predict outcomes among 2 cohorts of patients diagnosed with a single disease entity, acute myeloid leukemia in first complete remission, who underwent transplantation at either FHCRC or M. D.

Prognostic factors for outcomes of patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndromes undergoing allogeneic progenitor cell transplantation.

Allogeneic progenitor cell transplantation is the only curative therapy for patients with refractory acute myelogenous leukemia or myelodysplastic syndromes. To identify prognostic factors in these patients, we performed a retrospective analysis of transplantation outcomes. Patients were selected if they had undergone an allogeneic transplantation between January 1988 and January 2002 and were not in remission or first untreated relapse at the time of transplantation.

Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation.

Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32).

Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS.

Postulating favorable antileukemic effect with improved safety, we used intravenous busulfan and fludarabine as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Fludarabine 40 mg/m2 and intravenous busulfan 130 mg/m2 were given once daily for 4 days, with tacrolimus-methotrexate as graft-versus-host disease (GVHD) prophylaxis. We treated 74 patients with AML and 22 patients with MDS; patients had a median age of 45 years (range, 19-66 years).

Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters.

Hemorrhagic cystitis (HC) remains a common complication of allogeneic blood and marrow transplantation. Previous analyses of risk factors for this complication were performed in heterogeneous populations, with dissimilar diagnosis and conditioning regimens. We postulated that HC is more prevalent in matched unrelated donor (MUD) and unrelated cord blood (UCB) transplantations than in matched related donor (MRD) transplantations.

Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years.

Hematopoietic stem cell transplantation from unrelated donors is an effective treatment for myeloid malignancies, but its use is usually restricted to young patients without comorbidities. The development of reduced-intensity preparative regimens has allowed the extension of this form of treatment to older and medically infirm patients. We assessed the outcomes of patients older than 54 years who received unrelated donor transplants for the treatment of myeloid malignancies in our institution.

Treatment of relapsing refractory diffuse large cell lymphoma after matched unrelated donor bone marrow transplant with immunosuppression withdrawal and rituximab.

A 31-year-old man with a diffuse large-cell lymphoma in first refractory relapse received a bone marrow transplant (BMT) from a matched unrelated donor using CAMPATH-1H, carmustine, etoposide, cytarabine and melphalan as conditioning regimen, and methotrexate and tacrolimus for graft-versus-host disease (GVHD) prophylaxis. The transplant was complicated by grade II skin acute GVHD. Lymphoma relapse occurred 4 months post-transplant.

Long-term follow-up of a phase I study of high-dose decitabine, busulfan, and cyclophosphamide plus allogeneic transplantation for the treatment of patients with leukemias.

Background: Decitabine is a hypomethylating agent that has activity in patients with leukemia. The authors combined decitabine with busulfan and cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation.

Methods: Patients with high-risk acute myeloid leukemia (AML) (n = 12 patients); chronic myelomonocytic leukemia (CMML) (n = 1 patient); acute lymphocytic leukemia (ALL) (n = 1 patient); or late chronic phase, accelerated, or blastic phase chronic myelogenous leukemia (n = 9 patients) were eligible for the study.

Nonablative stem cell transplantation for older patients with acute leukemias and myelodysplastic syndromes.

High-dose chemoradiotherapy with allogeneic bone marrow or peripheral blood stem cell transplantation (SCT) is a potentially curative treatment for advanced or poor-prognosis hematological malignancies. This procedure was initially considered as a means to deliver supralethal doses of chemotherapy and radiation for the eradication of the malignancy, but it has subsequently become apparent that much of the therapeutic benefit of SCT relates to an associated immune-mediated graft-versus-leukemia (GVL) effect. Additionally, due to the increased risk of morbidity and graft-versus-host disease (GVHD) that occurs with advanced age, the use of standard myeloablative preparative regimens with allogeneic progenitor cell transplantation has been generally limited to younger patients in good medical condition.