Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma.

Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point.

A randomized study of melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative regimen for patients with multiple myeloma undergoing auto-SCT.

We aimed to examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m(2) (mel200) vs 280 mg/m(2) (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (⩾nCR).

A phase I study of decitabine and rapamycin in relapsed/refractory AML.

A phase I study utilizing decitabine (DAC) followed by the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, in patients with relapsed/refractory adult AML was undertaken to assess safety and feasibility. Patients received DAC 20mg/m(2) intravenously daily for 5 days followed by rapamycin from day 6 to day 25 at doses of 2 mg, 4 mg, and 6 mg/day in a standard 3+3 dose escalation design. Twelve patients completed treatment for safety evaluation.

Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines.

In this work, effects of bortezomib on apoptosis, clonal progenitor growth, cytokine production, and NF-κB expression in patients with MDS with cytopenias requiring transfusion support are examined. Bortezomib increased apoptosis in marrow mononuclear cells but had no effects on CFU-GM, BFU-E, or CFU-L content. No consistent effects on NF-κB activation in vivo were noted.

A Phase I trial: dose escalation of melphalan in the "BEAM" regimen using amifostine cytoprotection.

With the eventual goal of reducing relapse and thus improving overall survival in selected lymphoma patients, a Phase I study was performed using the cytoprotectant amifostine to permit safe dose-augmentation of melphalan in the carmustine (BCNU), etoposide, cytarabine (arabinosylcytosine), and melphalan (BEAM) regimen before autologous hematopoietic stem cell transplantation. Between 30 July 2003 and 25 November 2008, a total of 32 lymphoma patients were entered, of which 28 were evaluable. We found the melphalan dose in BEAM could be safely escalated to at least 260 mg/m², a substantial increase from the usual dose of 140 mg/m² in BEAM while the trial was terminated early due to poor accrual, no maximal tolerated dose or dose-limiting toxicity was found.

Phase I study of cladribine, cytarabine (Ara-C), granulocyte colony stimulating factor (G-CSF) (CLAG Regimen) and simultaneous escalating doses of imatinib mesylate (Gleevec) in relapsed/refractory AML.

Receptor activated tyrosine kinases such as c-kit, c-fms and PDGFR are known targets of inhibition by imatinib mesylate (Gleevec) and are expressed on AML blasts. Marrow stromal cells and monocytes express KIT ligand, M-CSF and PDGF and are therefore capable of activating survival pathways in these leukemic cells. Given the synergy in vitro between Ara-C and imatinib mesylate on AML cell growth inhibition, we initiated a Phase I study combining CLAG+imatinib mesylate in AML patients.

Apoptosis and complement-mediated lysis of myeloma cells by polyclonal rabbit antithymocyte globulin.

Current monoclonal antibody therapies for multiple myeloma have had limited success, perhaps due to narrow target specificity. We have previously described the ability of polyclonal rabbit antithymocyte globulin (rATG) to induce caspase- and cathepsin-mediated apoptosis in human B and plasma cells. We now extend this observation to myeloma cells.

Phase I study for poor-prognosis lymphoma: augmentation of the "BEAM" regimen with escalating dose melphalan using amifostine cytoprotection and autologous hematopoietic stem cell transplantation--a preliminary report.

We and others have previously shown that the use of amifostine (Ethyol; MedImmune Inc, Gaithersburg, MD) can ameliorate certain regimen-related toxicities of high-dose melphalan (HD-MEL) in the autologous hematopoietic stem cell transplant setting. Our recent experience indicated that the maximum tolerated dose of HD-MEL plus autologous hematopoietic stem cell transplant could be increased from approximately 200 mg/m2 to at least 280 mg/m2 with amifostine. Although a dose-limiting toxicity was not clearly identified, atrial fibrillation was noted in several patients.

Donor cell myelodysplastic syndrome after allogeneic stem cell transplantation responding to donor lymphocyte infusion: case report and literature review.

Allogeneic hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for patients with myelodysplastic syndrome (MDS). Relapses after transplantation however, are not uncommon and are usually due to re-emergence of a recipient derived, neoplastic, stem cell clone. We report a unique case of MDS recurring 5 months after non-myeloablative, sibling, allogeneic SCT.

Oral valacyclovir versus intravenous acyclovir in preventing herpes simplex virus infections in autologous stem cell transplant recipients.

Patients who are seropositive for herpes simplex virus (HSV) and are undergoing autologous marrow or peripheral blood stem cell transplantation require prophylaxis for HSV infection. Most prophylaxis regimens have used intravenous acyclovir (ACY). Oral valacyclovir (VAL), the L-valyl ester of ACY, can be used to achieve plasma concentrations equivalent to levels achieved with intravenous ACY.

Impact of mobilized blood progenitor cell quality determined by the CFU-GM/CD34+ ratio on rapid engraftment after blood stem cell transplantation.

To find a parameter to predict the quality of collected mobilized CD34+ blood as hemopoietic reconstituting cells, the ratio of CFU-GM to CD34+ cells was examined. One hundred six consecutive patients who underwent blood stem cell transplantation at the University of Rochester from 01/01/99 to 12/31/99 were examined retrospectively for the number of days to reach an absolute neutrophil count of 500 or 1000 cells/microl and an absolute platelet count of 20,000 or 50,000 cells/microl without transfusion support as measures of engraftment. Linear regression analyses were conducted to determine factors influencing engraftment.

CD-20 expression in post-transplant lymphoproliferative disorders: treatment with rituximab.

B-cell lymphoproliferative disorders are rare but serious complications of solid organ and bone marrow transplantation. We report that these tumors frequently express the CD-20 antigen, and immunotherapy directed at this antigen may be a well-tolerated and effective treatment.

Autoimmune thrombocytopenic purpura complicating lymphoproliferative disorders.

Thrombocytopenia in patients with lymphoproliferative disorders is usually multifactorial. In some patients, peripheral destruction of platelets by platelet autoantibodies may account in part for the thrombocytopenia. However, the diagnosis of autoimmune thrombocytopenic purpura in this group of patients can be difficult due to the splenomegaly and compromised bone marrows in some of these patients.