Alemtuzumab (Campath-1H) for treatment of lymphoid malignancies in the age of nonmyeloablative conditioning?

Hale, Geoff; Slavin, Shimon; Goldman, JM; Mackinnon, Stephen; Giralt, Sergío; Waldmann, Herman

doi:10.1038/sj.bmt.1703733

Cited by 39 publications

(19 citation statements)

References 59 publications

(49 reference statements)

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“…The repression of these genes can now be assigned at least partially to EBNA-2 functions. Since CD52 is a target for antibody-based chemotherapy of lymphoid malignancies, potential therapeutic implications might arise from our findings (15). The repression of T-cell leukemia I oncogene (TCL1A) by EBNA-2 was unex- pected since TCL1A has recently been described as an EBVinduced gene (30).…”

Section: Resultsmentioning

confidence: 92%

Cellular Target Genes of Epstein-Barr Virus Nuclear Antigen 2

Maier¹,

Staffler²,

Hartmann³

et al. 2006

J Virol

112

140

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Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) is a key determinant in the EBV-driven B-cell growth transformation process. By activating an array of viral and cellular target genes, EBNA-2 initiates a cascade of events which ultimately cause cell cycle entry and the proliferation of the infected B cell. In order to identify cellular target genes that respond to EBNA-2 in the absence of other viral factors, we have performed a comprehensive search for EBNA-2 target genes in two EBV-negative B-cell lines. This screen identified 311 EBNA-2-induced and 239 EBNA-2-repressed genes that were significantly regulated in either one or both cell lines. The activation of most of these genes had not previously been attributed to EBNA-2 function and will be relevant for the identification of EBNA-2-specific contributions to EBV-associated malignancies. The diverse spectrum of EBNA-2 target genes described in this study reflects the broad spectrum of EBNA-2 functions involved in virus-host interactions, including cell signaling molecules, adapters, genes involved in cell cycle regulation, and chemokines.

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Section: Resultsmentioning

confidence: 92%

Cellular Target Genes of Epstein-Barr Virus Nuclear Antigen 2

Maier¹,

Staffler²,

Hartmann³

et al. 2006

J Virol

112

140

View full text Add to dashboard Cite

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“…Chronic GVHD developed in 17 of 39 evaluable patients; 7 were scored as extensive. Such low aGVHD rates have also been reported for alemtuzumab at a dose of 100 mg. 27 We found very good early disease control, especially in the AML group: 10 of 14 evaluable patients achieved CR at one month. Of note, 12 were transplanted in uncontrolled disease.…”

Section: Discussionmentioning

confidence: 87%

A fludarabine, thiotepa reduced toxicity conditioning regimen designed specifically for allogeneic second haematopoietic cell transplantation after failure of previous autologous or allogeneic transplantation

Grüllich

Bertz

Spyridonidis

et al. 2008

Bone Marrow Transplant

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We present a phase II study of fludarabine 5 Â 30 mg/m 2 , thiotepa 3 Â 5 mg/kg as preparative regimen specifically for allogeneic second haematopoietic stem cell transplantation (HCT) after failure of previous HCT. Forty-nine patients (median age 52 years, range 27-68) received an allogeneic second HCT after failed autologous (n ¼ 29) or allogeneic (n ¼ 20) HCT. Diagnoses were AML (n ¼ 18), ALL (n ¼ 3), multiple myeloma (n ¼ 11), lymphoma (n ¼ 16) and CML (n ¼ 1). GVHD prophylaxis consisted of CYA and mainly low dose alemtuzumab (40 mg). The median follow-up for patients alive is 528 days (range 217-1344). In 43 of 49 (88%) evaluable patients response rates were CR ¼ 19, PR ¼ 14 and SD ¼ 10 at one month. At one year, the probability (95% confidence interval) of relapse is 55.1 (38.2-72)% and the nonrelapse mortality (NRM) is 29 (14.2-44.4)%. Estimated survival at one year is 42.6 (28.7-56.6)% and event free survival is 38.1 (24.4-51.8)%. Survival was significantly better for patients experiencing relapse beyond one year, than for patients relapsing within one year from first transplantation (51.2 (33.5-68.9)% vs 27 (7-48.5)%; P ¼ 0.013). We conclude that this regimen is feasible and well tolerated for allogeneic second HCT.

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“…Myeloablative allogeneic HSCT in CLL has a transplantation-related mortality (TRM) rate of approximately 50% (Flinn and Vogelsang, 1998;Hale et al, 2002). Acute and chronic graft-versus-host disease (aGVHD, cGVHD) remain significant causes of morbidity and mortality.…”

Section: Alemtuzumab In Autologous Stem Cell Transplantationmentioning

confidence: 99%