Over 1,000 patients with chronic granulocytic leukemia (CGL) have been given allogeneic bone marr... more Over 1,000 patients with chronic granulocytic leukemia (CGL) have been given allogeneic bone marrow transplantation (BMT) in less than 10 years (Fefer, 1979, worldwide 1986), of which 455 by the IBMTR, 672 by the EBMT (with some overlap with the former) and 198 from Seattle, and some firm conclusions have been reached, while other aspects remain or have become controversial. It is now firmly established that younger patients in chronic phase (CP) do better than older ones, although the upper age limit is not defined. The hope that BMT could be successfully performed in the accelerated phase, thus allowing the postponement of a potentially hazardous procedure until it becomes unescapable, has been shown to be fallacious. Indeed, a significant difference in survival according to whether BMT was performed 'early' or 'late' in CP has been found in Seattle, but not confirmed by the IBMTR report. The treatment of the spleen (splenectomy, radiation, none) was found not to influence the outcome by the EBMT, but the same group is conducting a second, more extensive randomized study. Depletion of postthymic T lymphocytes is an efficient procedure to reduce graft-versus-host disease, and thus to facilitate non-HLA identical BMT, but the significant and distressing augmentation of relapses, both cytogenetic and clinical, reported by the majority of the clinical studies cast grave doubts on its utility, at least in its present form.
La Leucemia Mieloide Cronica (LMC) es una enfermedad clonal, originada en las celulas troncales h... more La Leucemia Mieloide Cronica (LMC) es una enfermedad clonal, originada en las celulas troncales hematopoyeticas y caracterizada por la presencia del cromosoma Philadelphia (Ph) y su producto oncoproteico p210Bcr-Abl. Esta proteina presenta una incrementada y constitutiva actividad tirosina cinasa, esencial para la transformacion maligna, la cual altera propiedades celulares como la adhesion, proliferacion y apoptosis. Historicamente la LMC ha sido tratada con diferentes agentes, que van desde arsenico hasta trasplante de celulas hematopoyeticas, pasando por diversas sustancias quimicas (busulfan, hidroxiurea, citarabina), biomoduladores (IFN-α, IFNα -PEG) y moleculas generadas por diseno (imatinib, nilotinib, dasatinib). Todas estas moleculas ejercen actividades especificas sobre las celulas hematopoyeticas y conducen a diversas respuestas clinicas y biologicas. En esta revision se pretende dar una vision general sobre la hematopoyesis en LMC y sus implicaciones en las principales opciones de tratamiento
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
Chronic Myeloid Leukaemia (CML) is a clonal disease, originated at the level of Hematopoietic Ste... more Chronic Myeloid Leukaemia (CML) is a clonal disease, originated at the level of Hematopoietic Stem Cells (HSC) and characterized by the presence of the Philadelphia (Ph) chromosome and its oncogenic product p210(BcrAbl). Such a protein has been shown to be essential for malignant transformation, since it is capable of altering cell adhesion, proliferation and apoptosis. Historically, CML has been treated by using different approaches: arsenic (in the early days), a variety of chemical agents (busulfan, hydroxyurea, cytarabine), cytokines (IFN-alpha, IFNalpha-PEG), hematopoietic cell transplant (HCT), and more recently drugs generated by design (imatinib, nilotinib, dasatinib). All these molecules exert specific effects on HSC and lead to a variety of clinical and biological responses. In this article, we present an overview about hematopoiesis in CML and its implications in the treatment of this disease.
It has been suggested that type of chimeric mRNA is associated with differences in the clinical a... more It has been suggested that type of chimeric mRNA is associated with differences in the clinical and hematologic characteristics of chronic myeloid leukemia (CML). However, prognostic value of type of chimeric mRNA bcr-xabl (b3a2 or b2a2) is still controversial. We analyzed 97 cases of Philadelphia-positive CML to determine mRNA type by reverse-polymerase chain reaction (RT-PCR) and its relationship with clinical features. We detected b3a2 bcr-abl transcripts in 27 (28%) cases, b2a2 in 57 (59%) cases, and 13 (13%) with both mRNA transcripts b3a2/b2a2. These frequencies were the total reverse of other reports. Age, sex, hemoglobin, and white-cell counts showed no significant difference for those with either b3a2 or b2a2 bcr-abl transcripts. However, platelet counts of b3a2 patients were significantly higher than those of b2a2 patients (743.3 vs 477.3 x 109/L; p = 0.01). In addition, in the subgroup of patients whose white-cell count at diagnosis was < 100 x 10(9)/L, those with b3a2...
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
Chronic myeloid leukemia (CML) is characterized by a chromosomal translocation t(9; 22) resulting... more Chronic myeloid leukemia (CML) is characterized by a chromosomal translocation t(9; 22) resulting in the chimeric ber-abl oncogene that encode for the p210 protein which has an increased tyrosine kinase activity. The fusion part of this protein contains a novel aminoacid sequence. If peptides derived from this leukemia-specific part of p210 are expressed in the context of HLA molecules on malignant cells this may elicit immunologically specific responses. Recent studies using synthetic peptides identical to the bcr-abl fusion region revealed that breakpoint specific peptides are capable of binding to the class I molecules HLA-A3, -A11 and -B8. It has been shown that individuals expressing HLA-A3 or HLA-B8 have a diminished risk for development of CML in Caucasoid populations. Other authors have reported a statistically significant increase in the frequency of Cw3 and Cw4 antigens in Causcasoids and European CML patients. These data suggested that Cw3 and Cw4 may be markers for CML s...
We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), N... more We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p &amp;amp;lt; 0.01). We observed a 1.7-fold increase in NK and NKT cells (p &amp;amp;lt; 0.009 and p &amp;amp;lt; 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p &amp;amp;lt; 0.004) and a 8.5-fold increase in type 1 DC (p &amp;amp;lt; 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.
In this study, we have assessed the in vitro growth of hematopoietic progenitor cells (HPC) from ... more In this study, we have assessed the in vitro growth of hematopoietic progenitor cells (HPC) from chronic myeloid leukemia (CML) patients that have recovered after different treatments. Bone marrow cells were obtained from 33 CML patients, including patients at diagnosis, before treatment (n=12), and patients that have achieved hematological remission (and in most cases a major cytogenetic response) after different therapeutic procedures (n=21), including patients treated with Interferon-alpha (IFN; n=5), imatinib mesylate (IMATINIB; n=8) and patients that received an allogeneic hematopoietic cell transplant (HCT; n=8). Marrow cells were enriched for CD34(+) cells and cultured in a serum- and stroma-free liquid culture system, supplemented with a combination of 8 recombinant cytokines. Normal samples were studied as controls. HPC from CML patients before therapy showed deficient proliferation and expansion potentials in culture (140-fold increase in nucleated cell number and 1.3-fold increase in colony-forming cell number) as compared to normal progenitors (1200-fold increase in nucleated cell number and 25-fold increase in colony-forming cell number). In contrast, HPC from patients treated with IMATINIB showed growth potentials similar to those of normal progenitors. Progenitors from patients after HCT also showed significant proliferation and expansion capacities. Interestingly, progenitors from IFN-treated patients showed proliferation and expansion kinetics similar to those of cells from untreated patients. These results indicate that, although treatment of CML patients with IFN, IMATINIB or HCT resulted in complete hematological remission (and a major cytogenetic response), only patients treated with IMATINIB and, to a lesser extent, with HCT showed a full hematopoietic recovery, as determined by the in vitro growth of HPC in our culture system.
Chronic myeloid leukemia (CML) is a hematological neoplasia that results from the transformation ... more Chronic myeloid leukemia (CML) is a hematological neoplasia that results from the transformation of a hematopoietic stem cell. It is characterized by the expansion of the myeloid lineage, which results in the accumulation of mature and immature granulocytes in peripheral blood and bone marrow. However, when CML marrow cells are cultured in Dexter-type long-term cultures (LTMC) hematopoiesis is defective and can be sustained for only a few weeks. One possible explanation for the deficient growth of hematopoietic cells in CML LTMC is that some factors that act as key regulators of hematopoiesis are absent in this experimental system. Thus, we tested this hypothesis by adding recombinant cytokines to these cultures. As a first approach, we added recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), rhGranulocyte-CSF (rhG-CSF) and rhErythropoietin (rhEPO); each factor was added individually once a week. Addition of rhGM-CSF and rhG-CSF resulted in a significant increase in the levels of nucleated cells and myeloid progenitors; the highest effects were seen in the presence of rhGM-CSF. Interestingly, such a cytokine also induced a significant decrease in the levels of erythroid progenitors. Recombinant hEPO had no significant effects on nucleated cells or myeloid progenitors, however, it induced a significant, although transient, increase in the levels of erythroid cells. The above results indicate that the hematopoietic regulators used here (rhGM-CSF, rhG-CSF and rhEPO) are capable of stimulating the growth of hematopoietic cells in LTMC from CML patients. Thus, this study demonstrates that it is, indeed, possible to manipulate CML LTMC by the addition of recombinant cytokines; this observation may be of particular relevance, since this in vitro experimental system has already been used as a method for purging of leukemic cells in autologous transplant settings. By using specific recombinant hematopoietic modulators it might be possible to make LTMC a more efficient system for such a clinical purpose.
Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelo... more Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelomas. Between September 1990 and November 2000, among 540 patients with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found high frequencies of female patients (62 percent), Bence Jones proteinuria (79 percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42 percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21 percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)-microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71 percent, respectively. Four patients were treated with vincristine, melphalan, cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine, adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2) plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other clinical characteristics were comparable among the three groups. Complete plus partial responses were achieved in one and six patients treated with VMCPA and M-80, respectively. All patients treated with VAD failed to respond to treatment. Patients receiving the M-80 regimen experienced higher platelet toxicity (P=0.05), vomiting (P&amp;amp;lt;0.0003), and mucositis. Also, the need for red blood cell transfusions was higher in the M-80 group. Median overall survival was 60 days. Overall survival was better in patients achieving complete or partial response. In conclusion, our study illustrates that intermediate doses of melphalan plus dexamethasone are an effective chemotherapy regimen for this aggressive disease. Response to treatment is the only prognostic factor for survival in these patients.
... Alejandro Rosas-Cabral,*,** Manuel Martínez-Mancilla,**** Manuel Ayala-Sánchez,** Jorge Vela-... more ... Alejandro Rosas-Cabral,*,** Manuel Martínez-Mancilla,**** Manuel Ayala-Sánchez,** Jorge Vela-Ojeda,** Patricia Bahena-Reséndiz,** Manuel Vadillo ... Hochhaus A, Lin F, Rieter A, Skladny H, Masson PJ, Van Rhee F, Shepherd PC, Allan N, Hehlmann R, Goldman JM ...
Over 1,000 patients with chronic granulocytic leukemia (CGL) have been given allogeneic bone marr... more Over 1,000 patients with chronic granulocytic leukemia (CGL) have been given allogeneic bone marrow transplantation (BMT) in less than 10 years (Fefer, 1979, worldwide 1986), of which 455 by the IBMTR, 672 by the EBMT (with some overlap with the former) and 198 from Seattle, and some firm conclusions have been reached, while other aspects remain or have become controversial. It is now firmly established that younger patients in chronic phase (CP) do better than older ones, although the upper age limit is not defined. The hope that BMT could be successfully performed in the accelerated phase, thus allowing the postponement of a potentially hazardous procedure until it becomes unescapable, has been shown to be fallacious. Indeed, a significant difference in survival according to whether BMT was performed 'early' or 'late' in CP has been found in Seattle, but not confirmed by the IBMTR report. The treatment of the spleen (splenectomy, radiation, none) was found not to influence the outcome by the EBMT, but the same group is conducting a second, more extensive randomized study. Depletion of postthymic T lymphocytes is an efficient procedure to reduce graft-versus-host disease, and thus to facilitate non-HLA identical BMT, but the significant and distressing augmentation of relapses, both cytogenetic and clinical, reported by the majority of the clinical studies cast grave doubts on its utility, at least in its present form.
La Leucemia Mieloide Cronica (LMC) es una enfermedad clonal, originada en las celulas troncales h... more La Leucemia Mieloide Cronica (LMC) es una enfermedad clonal, originada en las celulas troncales hematopoyeticas y caracterizada por la presencia del cromosoma Philadelphia (Ph) y su producto oncoproteico p210Bcr-Abl. Esta proteina presenta una incrementada y constitutiva actividad tirosina cinasa, esencial para la transformacion maligna, la cual altera propiedades celulares como la adhesion, proliferacion y apoptosis. Historicamente la LMC ha sido tratada con diferentes agentes, que van desde arsenico hasta trasplante de celulas hematopoyeticas, pasando por diversas sustancias quimicas (busulfan, hidroxiurea, citarabina), biomoduladores (IFN-α, IFNα -PEG) y moleculas generadas por diseno (imatinib, nilotinib, dasatinib). Todas estas moleculas ejercen actividades especificas sobre las celulas hematopoyeticas y conducen a diversas respuestas clinicas y biologicas. En esta revision se pretende dar una vision general sobre la hematopoyesis en LMC y sus implicaciones en las principales opciones de tratamiento
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
Chronic Myeloid Leukaemia (CML) is a clonal disease, originated at the level of Hematopoietic Ste... more Chronic Myeloid Leukaemia (CML) is a clonal disease, originated at the level of Hematopoietic Stem Cells (HSC) and characterized by the presence of the Philadelphia (Ph) chromosome and its oncogenic product p210(BcrAbl). Such a protein has been shown to be essential for malignant transformation, since it is capable of altering cell adhesion, proliferation and apoptosis. Historically, CML has been treated by using different approaches: arsenic (in the early days), a variety of chemical agents (busulfan, hydroxyurea, cytarabine), cytokines (IFN-alpha, IFNalpha-PEG), hematopoietic cell transplant (HCT), and more recently drugs generated by design (imatinib, nilotinib, dasatinib). All these molecules exert specific effects on HSC and lead to a variety of clinical and biological responses. In this article, we present an overview about hematopoiesis in CML and its implications in the treatment of this disease.
It has been suggested that type of chimeric mRNA is associated with differences in the clinical a... more It has been suggested that type of chimeric mRNA is associated with differences in the clinical and hematologic characteristics of chronic myeloid leukemia (CML). However, prognostic value of type of chimeric mRNA bcr-xabl (b3a2 or b2a2) is still controversial. We analyzed 97 cases of Philadelphia-positive CML to determine mRNA type by reverse-polymerase chain reaction (RT-PCR) and its relationship with clinical features. We detected b3a2 bcr-abl transcripts in 27 (28%) cases, b2a2 in 57 (59%) cases, and 13 (13%) with both mRNA transcripts b3a2/b2a2. These frequencies were the total reverse of other reports. Age, sex, hemoglobin, and white-cell counts showed no significant difference for those with either b3a2 or b2a2 bcr-abl transcripts. However, platelet counts of b3a2 patients were significantly higher than those of b2a2 patients (743.3 vs 477.3 x 109/L; p = 0.01). In addition, in the subgroup of patients whose white-cell count at diagnosis was < 100 x 10(9)/L, those with b3a2...
Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
Chronic myeloid leukemia (CML) is characterized by a chromosomal translocation t(9; 22) resulting... more Chronic myeloid leukemia (CML) is characterized by a chromosomal translocation t(9; 22) resulting in the chimeric ber-abl oncogene that encode for the p210 protein which has an increased tyrosine kinase activity. The fusion part of this protein contains a novel aminoacid sequence. If peptides derived from this leukemia-specific part of p210 are expressed in the context of HLA molecules on malignant cells this may elicit immunologically specific responses. Recent studies using synthetic peptides identical to the bcr-abl fusion region revealed that breakpoint specific peptides are capable of binding to the class I molecules HLA-A3, -A11 and -B8. It has been shown that individuals expressing HLA-A3 or HLA-B8 have a diminished risk for development of CML in Caucasoid populations. Other authors have reported a statistically significant increase in the frequency of Cw3 and Cw4 antigens in Causcasoids and European CML patients. These data suggested that Cw3 and Cw4 may be markers for CML s...
We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), N... more We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p &amp;amp;lt; 0.01). We observed a 1.7-fold increase in NK and NKT cells (p &amp;amp;lt; 0.009 and p &amp;amp;lt; 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p &amp;amp;lt; 0.004) and a 8.5-fold increase in type 1 DC (p &amp;amp;lt; 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.
In this study, we have assessed the in vitro growth of hematopoietic progenitor cells (HPC) from ... more In this study, we have assessed the in vitro growth of hematopoietic progenitor cells (HPC) from chronic myeloid leukemia (CML) patients that have recovered after different treatments. Bone marrow cells were obtained from 33 CML patients, including patients at diagnosis, before treatment (n=12), and patients that have achieved hematological remission (and in most cases a major cytogenetic response) after different therapeutic procedures (n=21), including patients treated with Interferon-alpha (IFN; n=5), imatinib mesylate (IMATINIB; n=8) and patients that received an allogeneic hematopoietic cell transplant (HCT; n=8). Marrow cells were enriched for CD34(+) cells and cultured in a serum- and stroma-free liquid culture system, supplemented with a combination of 8 recombinant cytokines. Normal samples were studied as controls. HPC from CML patients before therapy showed deficient proliferation and expansion potentials in culture (140-fold increase in nucleated cell number and 1.3-fold increase in colony-forming cell number) as compared to normal progenitors (1200-fold increase in nucleated cell number and 25-fold increase in colony-forming cell number). In contrast, HPC from patients treated with IMATINIB showed growth potentials similar to those of normal progenitors. Progenitors from patients after HCT also showed significant proliferation and expansion capacities. Interestingly, progenitors from IFN-treated patients showed proliferation and expansion kinetics similar to those of cells from untreated patients. These results indicate that, although treatment of CML patients with IFN, IMATINIB or HCT resulted in complete hematological remission (and a major cytogenetic response), only patients treated with IMATINIB and, to a lesser extent, with HCT showed a full hematopoietic recovery, as determined by the in vitro growth of HPC in our culture system.
Chronic myeloid leukemia (CML) is a hematological neoplasia that results from the transformation ... more Chronic myeloid leukemia (CML) is a hematological neoplasia that results from the transformation of a hematopoietic stem cell. It is characterized by the expansion of the myeloid lineage, which results in the accumulation of mature and immature granulocytes in peripheral blood and bone marrow. However, when CML marrow cells are cultured in Dexter-type long-term cultures (LTMC) hematopoiesis is defective and can be sustained for only a few weeks. One possible explanation for the deficient growth of hematopoietic cells in CML LTMC is that some factors that act as key regulators of hematopoiesis are absent in this experimental system. Thus, we tested this hypothesis by adding recombinant cytokines to these cultures. As a first approach, we added recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), rhGranulocyte-CSF (rhG-CSF) and rhErythropoietin (rhEPO); each factor was added individually once a week. Addition of rhGM-CSF and rhG-CSF resulted in a significant increase in the levels of nucleated cells and myeloid progenitors; the highest effects were seen in the presence of rhGM-CSF. Interestingly, such a cytokine also induced a significant decrease in the levels of erythroid progenitors. Recombinant hEPO had no significant effects on nucleated cells or myeloid progenitors, however, it induced a significant, although transient, increase in the levels of erythroid cells. The above results indicate that the hematopoietic regulators used here (rhGM-CSF, rhG-CSF and rhEPO) are capable of stimulating the growth of hematopoietic cells in LTMC from CML patients. Thus, this study demonstrates that it is, indeed, possible to manipulate CML LTMC by the addition of recombinant cytokines; this observation may be of particular relevance, since this in vitro experimental system has already been used as a method for purging of leukemic cells in autologous transplant settings. By using specific recombinant hematopoietic modulators it might be possible to make LTMC a more efficient system for such a clinical purpose.
Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelo... more Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelomas. Between September 1990 and November 2000, among 540 patients with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found high frequencies of female patients (62 percent), Bence Jones proteinuria (79 percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42 percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21 percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)-microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71 percent, respectively. Four patients were treated with vincristine, melphalan, cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine, adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2) plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other clinical characteristics were comparable among the three groups. Complete plus partial responses were achieved in one and six patients treated with VMCPA and M-80, respectively. All patients treated with VAD failed to respond to treatment. Patients receiving the M-80 regimen experienced higher platelet toxicity (P=0.05), vomiting (P&amp;amp;lt;0.0003), and mucositis. Also, the need for red blood cell transfusions was higher in the M-80 group. Median overall survival was 60 days. Overall survival was better in patients achieving complete or partial response. In conclusion, our study illustrates that intermediate doses of melphalan plus dexamethasone are an effective chemotherapy regimen for this aggressive disease. Response to treatment is the only prognostic factor for survival in these patients.
... Alejandro Rosas-Cabral,*,** Manuel Martínez-Mancilla,**** Manuel Ayala-Sánchez,** Jorge Vela-... more ... Alejandro Rosas-Cabral,*,** Manuel Martínez-Mancilla,**** Manuel Ayala-Sánchez,** Jorge Vela-Ojeda,** Patricia Bahena-Reséndiz,** Manuel Vadillo ... Hochhaus A, Lin F, Rieter A, Skladny H, Masson PJ, Van Rhee F, Shepherd PC, Allan N, Hehlmann R, Goldman JM ...
Uploads
Papers