Anthony S Stein

Publications (9)41.32 Total impact

• Article: Reduced intensity allogeneic hematopoietic stem cell transplantation for MDS using tacrolimus/sirolimus-based GVHD prophylaxis.

  Ryotaro Nakamura, Joycelynne M Palmer, Margaret R O'Donnell, Tracey Stiller, Sandra H Thomas, Joseph Chao, Joseph Alvarnas, Pablo M Parker, Vinod Pullarkat, Rodrigo Maegawa, Anthony S Stein, David S Snyder, Ravi Bhatia, Karen Chang, Shirong Wang, Ji-Lian Cai, David Senitzer, Stephen J Forman
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  ABSTRACT: We report a consecutive series of 59 patients with MDS who underwent reduced-intensity hematopoietic stem cell transplantation (RI-HSCT) with fludarabine/melphalan conditioning and tacrolimus/sirolimus-based GVHD prophylaxis. Two-year OS, EFS, and relapse incidences were 75.1%, 65.2%, and 20.9%, respectively. The cumulative incidence of non-relapse mortality at 100 days, 1 year, and 2 years was 3.4%, 8.5%, and 10.5%, respectively. The incidence of grade II-IV acute GVHD was 35.4%; grade III-IV was 18.6%. Forty of 55 evaluable patients developed chronic GVHD; of these 35 were extensive grade. This RI-HSCT protocol produces encouraging outcomes in MDS patients, and tacrolimus/sirolimus-based GVHD prophylaxis may contribute to that promising result.
  Leukemia research 06/2012; 36(9):1152-6. · 2.36 Impact Factor
• Article: A phase I study in adults of clofarabine combined with high-dose melphalan as reduced-intensity conditioning for allogeneic transplantation.

  Mark H Kirschbaum, Anthony S Stein, Leslie Popplewell, Maria Delioukina, Robert Chen, Ryotaro Nakamura, David Snyder, Joel Conrad, Simon F Lacey, Paul Frankel, Andrew Dagis, Auayporn Nademanee, Stephen J Forman
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  ABSTRACT: Clofarabine is a novel purine nucleoside analog with immunosuppressive and antileukemia activity. We performed a phase I study of the combination of clofarabine plus melphalan as a reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with acute myelogenous leukemia. Patients over age 18 in complete remission or with active disease (up to 50% marrow blasts) who had a matched related or unrelated donor were eligible. The conditioning regimen consisted of escalating doses of clofarabine plus melphalan, followed by allogeneic stem cell transplantation. Sixteen patients (median age, 63 years) were treated at 3 dose levels; 4 of these patients had primary induction failure, and 3 were in first relapse. One patient at dose level 2 and 1 patient at dose level 3 died of multiorgan toxicity; no other dose-limiting toxicities were seen. All other patients at both doses of clofarabine studied demonstrated complete engraftment by day 30, with a median time to absolute neutrophil count recovery of 14 days, and 16 days for platelet recovery. With a median follow-up of 17 months, only 2 patients relapsed, and 4 patients died. Clofarabine plus melphalan at dose level 2 is a well-tolerated conditioning regimen with activity in patients with advanced acute myelogenous leukemia.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2011; 18(3):432-40. · 3.15 Impact Factor
• Article: Reduced-intensity conditioning followed by peripheral blood stem cell transplantation for adult patients with high-risk acute lymphoblastic leukemia.

  Anthony S Stein, Joycelynne M Palmer, Margaret R O'Donnell, Neil M Kogut, Ricardo T Spielberger, Marilyn L Slovak, Ni-Chun Tsai, David Senitzer, David S Snyder, Sandra H Thomas, Stephen J Forman
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  ABSTRACT: Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT); however, it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine (Flu)/melphalan (Mel) prior to allogeneic peripheral blood stem cell transplantation (PBSCT) between 6/14/02 and 6/15/07 at the City of Hope. Indications for the RIC regimen were: (1) aged 50 years or older (42%), (2) compromised organ function (54%), or (3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 months for living patients. Both overall survival (OS) and disease-free survival (DFS) at 2 years was 61.5%. Relapse incidence was 21.1% and nonrelapse mortality (NRM) was 21.5% at 2 years. Chronic graft-versus-host (cGVHD) developed in 86% of evaluable patients. In this series, no significant correlations were made between outcomes and patient age, presence of Philadelphia chromosome, relatedness of donor source, or prior HCT. These high survival rates for high-risk ALL patients following RIC HCT may offer a promising option for patients not eligible for a standard myeloablative transplant.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2009; 15(11):1407-14. · 3.15 Impact Factor
• Article: Improved outcomes using tacrolimus/sirolimus for graft-versus-host disease prophylaxis with a reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplant as treatment of myelofibrosis.

  David S Snyder, Joycelynne Palmer, Karl Gaal, Anthony S Stein, Vinod Pullarkat, Firoozeh Sahebi, Nyana Vora, Ryotaro Nakamura, Stephen J Forman
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  ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity conditioning (RIC) regimens is a potentially curative treatment for patients (patients) with myelofibrosis (MF), as we and others have reported. Nonrelapse mortality (NRM) from graft-versus-host disease (GVHD) and other complications has limited the success of this approach. As part of an ongoing prospective research study at City of Hope, a combination of tacrolimus/sirolimus +/- methotrexate (MTX) for GVHD prophylaxis has become the standard treatment for our allogeneic HCT patients. In this report, we present results for 23 consecutive patients, including extended follow up for 9 patients previously reported who received cyclosporine (CsA)/mycophenolate moffetil (MMF)+/-MTX, and the current series of 14 patients who received tacrolimus/sirolimus+/-MTX, and evaluate the impact of the GVHD prophylaxis regimen on the outcomes. Median follow-up for alive patients was 29.0 months (9.5-97.0). The estimated 2-year overall survival (OS) for the CsA/MMF cohort was 55.6% (confidence interval 36.0, 71.3), and for the tacrolimus/sirolimus cohort it was 92.9% (63.3, 98.8) (P=.047). The probability of grade III or IV acute GVHD (aGVHD) was 60% for the CsA/MMF patients, and 10% for the tacrolimus/sirolimus group (P=.0102). No significant differences were seen for grade II to IV aGVHD in the 2 groups. We conclude that the combination of tacrolimus/sirolimus+/-MTX for GVHD prophylaxis in the setting of RIC HCT for MF appears to reduce the incidence of severe aGVHD and NRM, and leads to improved OS compared to CSA/MMF+/-MTX.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2009; 16(2):281-6. · 3.15 Impact Factor
• Chapter: Autologous Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

  Anthony S. Stein, Stephen J. Forman
  10/2007: pages 1221 - 1237; , ISBN: 9780470987070
• Article: Allogeneic hematopoietic cell transplantation following reduced intensity conditioning for treatment of myelofibrosis.

  David S Snyder, Joycelynne Palmer, Anthony S Stein, Vinod Pullarkat, Firoozeh Sahebi, Sandra Cohen, Nayana Vora, Karl Gaal, Ryo Nakamura, Stephen J Forman
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  ABSTRACT: This report describes our experience with reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using matched sibling and unrelated donors (MUDs) for treatment of myelofibrosis (MF). Nine patients with MF (median age, 54 years) were treated with RIC allogeneic HCT using MUDs for 7 of the 9 patients and sibling donors for 2 patients. By the Lille classification, 4 patients were characterized as having high risk, 4 as having intermediate risk, and 1 as having low risk. The RIC regimen consisted of fludarabine and a single dose of total body irradiation for the first patient and fludarabine/melphalan for the remaining 8 patients. Granulocyte colony-stimulating factor-primed peripheral blood stem cells (PBSCs) were used for all but 1 patient who received a total of 3 products because of graft failure, of which 2 were bone marrow cells and the third was PBSCs. Prophylaxis against graft-versus-host disease consisted of cyclosporin/mycophenolate with or without methotrexate. Seven patients were successfully engrafted with white blood cells, with an absolute neutrophil count > or =500 by a median of day +15 (range, 10-21 days). At the time of final fluorescence in situ hybridization and/or short tandem repeat analysis, 8 of 9 patients were chimeric, with 96%-100% donor cells and/or DNA. Five of the 9 patients were alive at the time of final contact, with a median follow-up of 32.2 months for the living patients. Overall survival probability at 1 year was 55.6% (95% confidence interval, 31.3%-77.4%). These results suggest that RIC MUD HCT using PBSCs can be an effective treatment for older patients with MF.
  Biology of Blood and Marrow Transplantation 12/2006; 12(11):1161-8. · 3.87 Impact Factor
• Article: Philadelphia chromosome-positive acute lymphoblastic leukemia secondary to chemoradiotherapy for Ewing sarcoma. Report of two cases and concise review of the literature.

  David S Snyder, Anthony S Stein, Margaret R O'Donnell, Karl Gaal, Marilyn L Slovak, Stephen J Forman
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  ABSTRACT: Survivors of childhood solid tumors including Ewing sarcoma (ES) have an increased risk of secondary malignant neoplasms (SMNs) as a consequence of exposure to chemotherapy and/or radiation (see: Bhatia S, Sklar C. Nat Rev Cancer 2002;2:124-132). The most common hematologic SMNs are myelodysplasia (MDS) and acute myelogenous leukemia (AML). Acute lymphoblastic leukemia (ALL) is uncommon in this patient population, and Philadelphia chromosome positive (Ph+) ALL in particular, is rare. We report herein two cases of young adult patients who were both diagnosed with Ph+ ALL 19 years after successful treatment for ES with combined modality therapy. A review of the relevant literature follows the case reports.
  American Journal of Hematology 02/2005; 78(1):74-8. · 4.67 Impact Factor
• Source

  Available from: ascpjournals.org

  Article: Prognostic impact of acute myeloid leukemia classification. Importance of detection of recurring cytogenetic abnormalities and multilineage dysplasia on survival.

  Daniel A Arber, Anthony S Stein, Nora H Carter, David Ikle, Stephen J Forman, Marilyn L Slovak
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  ABSTRACT: To evaluate the prognostic impact of acute myeloid leukemia (AML) classifications, specimens from 300 patients with 20% or more bone marrow myeloblast cells were studied. Specimens were classified according to the French-American-British Cooperative Group (FAB), the World Health Organization (WHO), the Realistic Pathologic Classification, and a cytogenetic risk group scheme. Cases with fewer than 30% blast cells did not have a 5-year survival significantly different from cases with 30% or more blast cells, and survival was similar for the low blast cell count group and cases with multilineage dysplasia and 30% or more blasts. Categories of AML with recurrent cytogenetic abnormalities of t(15;17), t(8;21), inv(16)/t(16;16), and 11q23 showed significant differences in 5-year survival. No significant difference was identified between AMLs arising from myelodysplasia and de novo AMLs with multilineage dysplasia, but all cases with multilineage dysplasia had a worse survival than all other AMLs and other AMLs without favorable cytogenetics. FAB types M0, M3, and M4Eo showed differences in survival compared with all other FAB types, with M0 showing a significant association with high-risk cytogenetics and 11q23 abnormalities. Other FAB groups and WHO AML, not otherwise categorized subgroups did not show survival differences. These findings suggest that the detection of recurring cytogenetic abnormalities and multilineage dysplasia are the most significant features of current AML classification.
  American Journal of Clinical Pathology 06/2003; 119(5):672-80. · 2.60 Impact Factor
• Article: Interleukin-2 after autologous stem-cell transplantation for adult patients with acute myeloid leukemia in first complete remission.

  Anthony S Stein, Margaret R O'Donnell, Marilyn L Slovak, David S Snyder, Auayporn P Nademanee, Pablo Parker, Arturo Molina, George Somlo, Henry C Fung, Amrita Krishnan, Roberto Rodriguez, Ricardo T Spielberger, Shirong Wang, Andrew Dagis, Nayana Vora, Daniel A Arber, Joyce C Niland, Stephen J Forman
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  ABSTRACT: To determine the disease-free survival (DFS) and toxicity of administering interleukin-2 (IL-2) immunotherapy early after autologous stem-cell transplantation (ASCT) to simulate a graft versus leukemia effect observed in allogeneic transplantation. Fifty-six patients with acute myeloid leukemia in first remission received a single consolidation of high-dose cytarabine-idarubicin at a median of 1.1 month postremission with the intent to proceed to ASCT and IL-2 9 x 10(6) U/m(2)/24 h for 4 days, followed by 10 days of IL-2 1.6 x 10(6) U/m(2)/24 h on hematologic recovery. Eighty-four percent of patients received the intended ASCT, and 68% of patients received IL-2 treatment. With a median follow-up of 39.4 months (range, 1.2 to 76.3 months), the 2-year cumulative probability of DFS for all 56 patients is 68% (95% confidence interval [CI], 55% to 80%) and 74% (95% CI, 57% to 85%) for the 39 patients undergoing IL-2 treatment after ASCT. The 2-year cumulative probability of DFS for favorable, intermediate, and unfavorable cytogenetics is 88% (95% CI, 59% to 97%), 48% (95% CI, 26% to 67%), and 70% (95% CI, 23% to 93%), respectively. Toxicities from IL-2 were mainly thrombocytopenia, leukopenia, fever, and fluid retention. Two septic deaths occurred during neutropenia, which includes one during consolidation and one during transplant, for an overall 4% mortality rate. These results suggest that a moderate dose of IL-2 after high-dose cytarabine-idarubicin-mobilized ASCT is associated with a low regimen-related toxicity and may improve DFS. A phase III study of IL-2 is now warranted.
  Journal of Clinical Oncology 03/2003; 21(4):615-23. · 18.37 Impact Factor