Speciality
Spotlight

 




 


Oncology


 

 






Clinical
Bone Marrow Transplant

   

  • Vermylen
    C, Cornu G, Ferster A, et al [ Univ of Louvain,
    Brussels, Belgium; Univ of Brussels, Belgium; Univ Hosp,
    Gent, Belgium; et al ]

    Haematopoietic Stem Cell Transplantation for Sickle
    Cell Anamia : The First 50 Patients Transplanted in
    Belgium


    Bone Marrow Transplant 22: 1-6, 1998

      

    Bone Marrow transplantation [BMT] for the treatment of
    sickle cell anemia is known however, this potentially
    dangerous procedure has been proposed for only severely
    affected children with sickle cell anemia.

      

    This study compared 36 children with morbid disease
    course compared with 14 children who had undergone
    transplant earlier in the disease course. The overall
    11-year survival rate of 93%, an event-free survival of
    82%, and disease free survival of 85%. Although the
    survival rates and apparent cure of disease were high in
    both groups. They were particularly good in low risk
    patients. The editor comments that this study proposed
    an early transplant in sickle cell disease, if a HLA
    identical sibling is available as in very young
    patients, the risks of both graft rejection and GVHD are
    low, and procedure related complications peculiar to
    sickle cell disease such as seizures and cerebrovascular
    accidents, should be less frequent in those without pre
    existing vascular disease.

       

  • Slavin
    S, Nagler A, Naparstek E, et al [ Hadassah Univ,
    Jerusalem; Ichilov Hosp, Tel Aviv, Israel ]

    Nonmyeloablative Stem Cell Transplantation and Cell
    Therapy as an Alternative to Conventional Bone Marrow
    Transplantation With Lethal Cytoreduction for the
    Treatment of Malignant and Nonmalignant Hematologic
    Disease


    Blood 91: 756-763, 1998

      

    The treatment of some of the malignant hematologic and
    genetic disease, myeloablative conditioning is
    considered mandatory first step for allogenic blood or
    marrow transplantation [BMT]. This study of 26 patients
    with standard indications for allogenic BMT underwent
    non myeloblative conditioning with fludarabine and
    anti-T-lymphocyte globulin and a low dose of busulfan
    was tolerated very well. Granulocyte-Colony-stimulating
    factor mobilized blood stem cell transplantation with
    standard- dose cyclosporin [ CYSA ] as only anti-graft-vs.-host-disease
    [GVHD] prophylaxis produced some stable partial
    chimerism in 9 patients and complete chimerism in 17.
    Severe GVHD leading to mortality occured in 4 patients,
    which was attributed to early withdrawl of CYSA. This
    innovative protocol represents a new approach for safer
    treatment of many clinical syndromes necessiating
    allogenic BMT. Transient mixed chimerism, which may
    protect the host from sever acute GVHD, may be
    effectively reversed after allogenic BMT with graded
    increments of donor lymphocyte infusion resulting in
    elimination of malignant or genetically abnormal clone.

      

  • Ueno
    NT, Rondon G, Mirza NQ, et al [ Univ of Texas, Houston ]

    Allogeneic Peripheral-Blood Progenitor-Cell (PBPC) Transplantation for Poor-Risk Patients with Metastatic
    Breast Cancer


    J Clin Oncol 16: 986-993, 1998

      

    Metastatic breast cancer especially those involving the
    liver or bone marrow is poor.

      

    This study of 42 patients with metastatic [liver or bone
    marrow] received high dose chemotherapy [
    cyclophosphamide, carmustine and thiotepa ] and
    allogenic PBPC transplantation. Graft vs-host disease
    prophylaxis was with cyclosporine or tacrolimus. One
    patient had complete remission, 5 partial remission and
    4 stable disease. Metastatic liver lesions regressed in
    2 patients with withdrawal of immunosuppressive therapy.
    Tumor regression in association with GVHD suggest graft
    vs tumor effects may occur against breast cancer.

         

  • Horowitz MM, and the German CML Study Group [Med College of Wisconsin, Milwaukee] 

    Survival with Bone Marrow Transplantation Versus Hydroxyurea or Interferon for Chronic Myelogenous Leukemia

    Blood 91: 1810-1819, 1998

       

    The treatment option for a young chronic myelogenous leukemia [CML] are hydroxyurea, interferon and HLA identified sibling transplant [BMT] although the best treatment is not yet known. This study of patients with CML who had received one of the above therapy were analyzed. At 18 months bone marrow transplantation had a high mortality where as 18-56 months mortality was similar in all groups. At 56 mortality was lower in BMT group. BMT done within one year of diagnosis had earlier survival advantage and those with intermediate and high risk prognostic factors had further greater and earlier survival advantage than those with low risk prognostic factors.

       

    In this study 20-30% failed to survive a year after BMT whereas annual mortality of about 10% in patients with medical treatment is known.

        

  • Hansen JA, Gooley TA, Martin PJ, et al [ Fred Hutchinson Cancer Research Ctr, Seattle]

    Bone Marrow transplants From Unrelated Donors for Patients with Chronic Myeloid Leukemia

    N Engl J Med 338: 962-968, 1998

      

    Chronic myeloid leukemia [CML] patients without HLA matched sibling underwent transplantation of marrow from unrelated donor its associated morbidity and mortality were studied in
    Seattle. Factors affecting survival included 1 or more year interval between diagnosis and transplantation. An HLA-DRB1 mismatch a high body weight index, and age above 50 years. The prophylactic use of fluconazole and ganciclovir improved survival. After correction of the above factors survival and relapse rates in CML patients undergoing transplantation either from HLA-matched for sibling or unrelated donors are comparable.

      

  • Aghajanjan C, Fennelly D, Shapiro F, et al [ Mem Sloan -Kettering Cancer Ctr, New York; St Vincents Hosp, Dublin, Ireland]

    Phase II Study of ” Dose -Dense” High-Dose Chemotherapy Treatment with Peripheral-Blood Progenitor-Cell
    (PBP) Support as Primary Treatment for Patients With Advanced Ovarian Cancer


    J Clin Oncol 16: 1852-1860, 1998

          

    This phase II pilot study of 21 patients with stage IIC to IV ovarian cancer received high dose chemotherapy regimen that included carboplatin, paclitaxel, and
    melphalan, each course rescued with PBP. This therapy was frequently complicated by severe toxicity. The response to high dose therapy also was dependent on volume of disease at the time of initiating chemotherapy. In patients with optimal disease the complete response was 55% compared with 13% in suboptimal stage III and IV. Currently there is no established role for high dose chemotherapy with PBP in any subset of patients with ovarian cancer.

         

  • Santini G, Salvagno L, Leoni P, et al [San Martino Hosp, Genova, Italy; Genova Univ, Italy; Gen Hosp, Padova, Italy; et al]

    VACOP-B VersusVACOP-B Plus Autologous Bone Marrow Transplantation for Advanced Diffuse Non-Hodgkin’s Lymphoma: Results of a Prospective Randomized Trial by the Non-Hodgkin’s Lymphoma Cooperative Study Group

    J Clin Oncol 16: 2796-2802, 1998

       

    This study of 124 patients with diffuse intermediate/high-grade non-Hodgkin’s lymphoma, stage II bulky, III & IV received etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [VACOP-B], with cisplatin, cytarabine, and dexamethasone as a salvage regimen and other arm received VACOP-B plus high dose therapy and autologous bone marrow transplantation.

         

    There was no difference in remission rates; overall survival and disease free survival between the two groups. In a subset of patients according to the international Prognostic Index, patients with intermediate high risk and high risk disease did have a significant improvement in disease free survival with the use of high dose therapy over standard chemotherapy. However, no significant difference in overall survival was noted.

          

  • Deeg HJ, Leisenring W, Storb R, et al [Fred Hutchinson Cancer Research Ctr, Seattle; Univ of Washington, Seattle]

    Long-Term Outcome After Marrow Transplantation for Severe Aplastic Anemia

    Blood 91: 3637-3645, 1998

       

    The retrospective review of 212 patients who underwent marrow transplantation for aplastic anemia at the Fred. Hutchinson Cancer Research Center and survival for more than 2 years underwent assessment for long term mobidity and mortality. The presence of chronic graft versus host disease predicted a lower 20 year survival and a lower performance status. It was also associated with chronic skin problems, pulmonary problem, and depression. Other long-term complications due to sterioids, included cataracts, aseptic necrosis of the bone. 

      

    Fertility was maintained in large number of these survivors.

         

  • Ratanatharathorn V, Nash RA, Przepiorka D, et al [Univ of Michigan, Ann Arbor; Fred Hutchinson Cancer Research Ctr, Seattle; MD Anderson Cancer Ctr, Houston; et al]

    Phase III Study Comparing Methotrexate and Tacrolimus [Prograf, FK506] with Methotrexate and Cyclosporine for Graft-Versus-Host Disease Prophylaxis After HLA-Identical Sibling Bone Marrow Transplantation

    Blood 92: 2303-2314, 1998

       

    Acute GVHD occurs in 40% to 50% of allogeneic bone marrow transplantation recipient. This phase III, open-label, randomized, multicenter study assigned 165 patients to tacrolimus + methotrexate and 164 patients to methotrexate + cyclosporine for GVHD prophylaxis after histocompatibility leukocyte antigen-identical sibling marrow transplantation in patients with hematologic malignancy. 

      

    The incidence of grade II through IV GVHD was significantly lower in tacrolimus than in cyclosporine recipients despite this reduction in grade II & IV GVHD the patient receiving tacrolimus had a significantly worse overall survival and disease free survival than clyclosporine recipients. This was attributed to regimen related 

    toxicities especially in patients with advanced disease status. The editor comments further studies are warranted, particularly in patients with advanced disease before this becomes the standard GVHD prophylaxis regimen.

         

  • Hansen JA, Gooley TA, Martin PJ, et al [ Fred Hutchinson Cancer Research Ctr, Seattle; Veterans Affairs Med Ctr, Seattle; Univ of Washington, Seattle]

    Bone Marrow Transplants From Unrelated Donors for Patients With Chronic Myeloid Leukemia

    N Engl J Med 338: 962-968, 1998

        

    Allogenic bone marrow transplantation remains the only curative therapy for patients with chronic myeloid leukemia. This study of 196 patients Philadelphia chromosome positive CML in chronic phase underwent marrow transplantation from unmatched unrelated donors and were monitored for a median of 5 years, 35% had acute graft versus host disease [grade III and IV ]. Factors affecting adversely the survival including one year or longer interval between diagnosis and transplantation, an HLA-DRB1 mismatch in a high body weight index and age exceeding to years. The prophylactic use of fluconazole and ganciclovir improved survival. Hence patients younger than 50 years undergoing transplant from HLA matched unrelated donor within one year of diagnosis have a 5 year survival estimate of 74%. These results compare with marrow transplantation from an HLA matched identical sibling.

         

  • Slavin S, Nagler A, Naparstek E, et al [Hadassah Univ Hosp, Jerusalem; Ichilov Hosp, Tel Aviv, Israel]

    Nonmyeloablative Stem Cell Transplantation and Cell Therapy as an Alternative to Conventional Bone Marrow Transplantation With Lethal Cytoreduction for the Treatment of Malignant and Nonmalignant Hematologic Disease

    Blood 91: 756-763, 1998

       

    The first step in preparation of allogenic blood or bone marrow transplantation is myeloablative conditioning however this is frequently associated with hazardous immediate and late complications. This study of 26 patients with standard indication for allogeneic BMT reviewed non myeloablative conditioning consisting of fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan was well tolerated.

      

    Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose cyclosporin as the only graft-vs.-host-disease [GVHD] prophylaxis produced stable transient mixed chimerism. Absolute neutrophil count of 0.5 x 109/L or greater were achieved within 10-32 days and platelet counts above 20 X 109/L within 35 days. 14 patients had no GVHD and 4 patients developed severe GVHD on discontinuation of cyclosporine resulting in death. The chimerism in these type of transplant is believed to protect the host from severe acute GVHD. This may be effectively revised with graded increments of donor lymphocyte infusions resulting in elimination of malignant or genetically abnormal progenitor cells of host origin.

      

    The minimal toxicity associated with this approach suggests that it may be applicable to a broader range of patients previously not eligible for allogeneic BMT.

         

  • Khouri IF, Keating M, Korbling M, et al [ Univ of Texas, Houston]

    Transplant-Lite: Induction of Graft-Versus-Malignancy Using Fludarabine-based Nonablative Chemotherapy and Allogeneic Blood Progenitor-Cell Transplantation as Treatment for Lymphoid Malignancies

    J Clin Oncol 16: 2817-2824c, 1998

       

    This study of 15 patients with chronic lymphocytic leukemia and lymphoma
    received treatment [average of three previous regimens]
    with fludarabine based regimen, as nonmyeloablative regimen to produce immunosuppression followed by allogeneic stem cells infusion from histocompatibility leukocyte antigen identical siblings. Prompt hematopoietic recovery occurred in all patients who had engraftment, 8 had complete remission and 3 had decreased tumor mass. Four patients received donor lymphocyte infusion to augment the graft -vs.-leukemia/lymphoma [GVL] effect & the clinical response observed. These results suggest that allogeneic nonmyeloablative transplantation allows engraftment and GVL against lymphoid malignancies is feasible. Patients with chemosensitive disease and low tumor burden may benefit from this approach.

        

  • Verdonck LF, Petersen EJ, Lokhorst HM, et al [ Univ Hosp Utrecht, The Netherlands]

    Donor Leukocyte Infusions for Recurrent Hematologic Malignancies After Allogeneic Bone Marrow Transplantation : Impact of Infused and Residual Donor T Cells

    Bone Marrow Transplant 22 :1057-1063, 1997

      

    Previous studies have shown that complete donor T-cell chimerism is needed for graft vs. leukemia effect patients with chronic myeloid leukemia and multiple myeloma who have relapses after bone marrow transplantation are likely to respond to donor leukocyte infusion [DLI] in patients with acute leukemia in full-blown relapse, tumor reduction is needed before DLI. Mixed T-cell chimeras respond as well as complete donor T-cell chimeras to DLI. The DLI can be associated with substantial toxicity, 22% mortality rate from GVHD in this study.

        

  • Milpied N, Gaillard F, Moreau P, et al [ Univ Hosp, Nantes, France]

    High-Dose Therapy with Stem Cell Transplantation for Mantle Cell Lymphoma : Results and Prognostic Factors, a Single Center Experience

    Bone Marrow Transplant 22: 645-650, 1998

      

    Mantle Cell Lymphoma [MCL] is diagnosed as discrete entity in the recent years. The median survival of patients with MCL is 40 months with conventional chemotherapy. In view of the poor prognosis, high dose chemotherapy with addition of stem cell transplantation has been studied in 16 patients with stage IV MCL and 12 with bone marrow involvement. At a median of 36 months, 15 patients were still alive and 11 had no evidence of disease progression, between 2 and 51 month, 7 patients’ disease progressed.

       

    Patients receiving total body irradiation as conditioning had a better 4 year overall and disease free survival. Patients with blastic histology did poor worse. 

       

    The editor comments that high dose chemotherapy although effective for patients with relapsed intermediate and high grade lymphomas is not the answer for patients with MCL.

          

  • Avash LJ, Elias A, Ibrahim J, et al [Harvard Med School, Boston; Wake Forest Univ, Winston-Salem, NC]

    High-Dose Multimodality Therapy with Autologous Stem-Cell Support for Stage IIIB Breast Carcinoma

    J Clin Oncol 16: 1000-1007, 1998

      

    Stage III locally advanced breast cancer is made up of a variety of tumor types.

      

    This study of 4 stage IIIA and 46 stage IIIB breast cancer patients underwent induction chemotherapy with doxorubicin 90mg/m2 with granulocyte colony-stimulating factor [G-CSF] followed by high dose
    cyclophosphamide, thiotepa and carboplatin  [CTCb] with peripheral blood progenitor cell [ PBPC] support, and autologous bone marrow transplantation [ABMT] and mastectomy plus local radiotherapy to some patients. Tamoxifen [10 mg] twice a day for ER or PR positive patients. At 30 months disease free survival rate is estimated at 64% . 32% experienced relapses mainly at distant site, at a median at 17 months from CTCb.

      

    The editor comments that the preliminary results from this trial are promising , however at this point it is difficult to compare the preliminary results from this trial to other more mature phase II trials.

           


 

 



 

 

Speciality Spotlight

 

 

Clinical Bone Marrow Transplant
   

  • Vermylen C, Cornu G, Ferster A, et al [ Univ of Louvain, Brussels, Belgium; Univ of Brussels, Belgium; Univ Hosp, Gent, Belgium; et al ]
    Haematopoietic Stem Cell Transplantation for Sickle Cell Anamia : The First 50 Patients Transplanted in Belgium
    Bone Marrow Transplant 22: 1-6, 1998
      
    Bone Marrow transplantation [BMT] for the treatment of sickle cell anemia is known however, this potentially dangerous procedure has been proposed for only severely affected children with sickle cell anemia.
      
    This study compared 36 children with morbid disease course compared with 14 children who had undergone transplant earlier in the disease course. The overall 11-year survival rate of 93%, an event-free survival of 82%, and disease free survival of 85%. Although the survival rates and apparent cure of disease were high in both groups. They were particularly good in low risk patients. The editor comments that this study proposed an early transplant in sickle cell disease, if a HLA identical sibling is available as in very young patients, the risks of both graft rejection and GVHD are low, and procedure related complications peculiar to sickle cell disease such as seizures and cerebrovascular accidents, should be less frequent in those without pre existing vascular disease.
       

  • Slavin S, Nagler A, Naparstek E, et al [ Hadassah Univ, Jerusalem; Ichilov Hosp, Tel Aviv, Israel ]
    Nonmyeloablative Stem Cell Transplantation and Cell Therapy as an Alternative to Conventional Bone Marrow Transplantation With Lethal Cytoreduction for the Treatment of Malignant and Nonmalignant Hematologic Disease
    Blood 91: 756-763, 1998
      
    The treatment of some of the malignant hematologic and genetic disease, myeloablative conditioning is considered mandatory first step for allogenic blood or marrow transplantation [BMT]. This study of 26 patients with standard indications for allogenic BMT underwent non myeloblative conditioning with fludarabine and anti-T-lymphocyte globulin and a low dose of busulfan was tolerated very well. Granulocyte-Colony-stimulating factor mobilized blood stem cell transplantation with standard- dose cyclosporin [ CYSA ] as only anti-graft-vs.-host-disease [GVHD] prophylaxis produced some stable partial chimerism in 9 patients and complete chimerism in 17. Severe GVHD leading to mortality occured in 4 patients, which was attributed to early withdrawl of CYSA. This innovative protocol represents a new approach for safer treatment of many clinical syndromes necessiating allogenic BMT. Transient mixed chimerism, which may protect the host from sever acute GVHD, may be effectively reversed after allogenic BMT with graded increments of donor lymphocyte infusion resulting in elimination of malignant or genetically abnormal clone.
      

  • Ueno NT, Rondon G, Mirza NQ, et al [ Univ of Texas, Houston ]
    Allogeneic Peripheral-Blood Progenitor-Cell (PBPC) Transplantation for Poor-Risk Patients with Metastatic Breast Cancer
    J Clin Oncol 16: 986-993, 1998
      
    Metastatic breast cancer especially those involving the liver or bone marrow is poor.
      
    This study of 42 patients with metastatic [liver or bone marrow] received high dose chemotherapy [ cyclophosphamide, carmustine and thiotepa ] and allogenic PBPC transplantation. Graft vs-host disease prophylaxis was with cyclosporine or tacrolimus. One patient had complete remission, 5 partial remission and 4 stable disease. Metastatic liver lesions regressed in 2 patients with withdrawal of immunosuppressive therapy. Tumor regression in association with GVHD suggest graft vs tumor effects may occur against breast cancer.
         

  • Horowitz MM, and the German CML Study Group [Med College of Wisconsin, Milwaukee] 
    Survival with Bone Marrow Transplantation Versus Hydroxyurea or Interferon for Chronic Myelogenous Leukemia
    Blood 91: 1810-1819, 1998
       
    The treatment option for a young chronic myelogenous leukemia [CML] are hydroxyurea, interferon and HLA identified sibling transplant [BMT] although the best treatment is not yet known. This study of patients with CML who had received one of the above therapy were analyzed. At 18 months bone marrow transplantation had a high mortality where as 18-56 months mortality was similar in all groups. At 56 mortality was lower in BMT group. BMT done within one year of diagnosis had earlier survival advantage and those with intermediate and high risk prognostic factors had further greater and earlier survival advantage than those with low risk prognostic factors.
       
    In this study 20-30% failed to survive a year after BMT whereas annual mortality of about 10% in patients with medical treatment is known.
        

  • Hansen JA, Gooley TA, Martin PJ, et al [ Fred Hutchinson Cancer Research Ctr, Seattle]
    Bone Marrow transplants From Unrelated Donors for Patients with Chronic Myeloid Leukemia
    N Engl J Med 338: 962-968, 1998
      
    Chronic myeloid leukemia [CML] patients without HLA matched sibling underwent transplantation of marrow from unrelated donor its associated morbidity and mortality were studied in Seattle. Factors affecting survival included 1 or more year interval between diagnosis and transplantation. An HLA-DRB1 mismatch a high body weight index, and age above 50 years. The prophylactic use of fluconazole and ganciclovir improved survival. After correction of the above factors survival and relapse rates in CML patients undergoing transplantation either from HLA-matched for sibling or unrelated donors are comparable.
      

  • Aghajanjan C, Fennelly D, Shapiro F, et al [ Mem Sloan -Kettering Cancer Ctr, New York; St Vincents Hosp, Dublin, Ireland]
    Phase II Study of ” Dose -Dense” High-Dose Chemotherapy Treatment with Peripheral-Blood Progenitor-Cell (PBP) Support as Primary Treatment for Patients With Advanced Ovarian Cancer
    J Clin Oncol 16: 1852-1860, 1998
          
    This phase II pilot study of 21 patients with stage IIC to IV ovarian cancer received high dose chemotherapy regimen that included carboplatin, paclitaxel, and melphalan, each course rescued with PBP. This therapy was frequently complicated by severe toxicity. The response to high dose therapy also was dependent on volume of disease at the time of initiating chemotherapy. In patients with optimal disease the complete response was 55% compared with 13% in suboptimal stage III and IV. Currently there is no established role for high dose chemotherapy with PBP in any subset of patients with ovarian cancer.
         

  • Santini G, Salvagno L, Leoni P, et al [San Martino Hosp, Genova, Italy; Genova Univ, Italy; Gen Hosp, Padova, Italy; et al]
    VACOP-B VersusVACOP-B Plus Autologous Bone Marrow Transplantation for Advanced Diffuse Non-Hodgkin’s Lymphoma: Results of a Prospective Randomized Trial by the Non-Hodgkin’s Lymphoma Cooperative Study Group
    J Clin Oncol 16: 2796-2802, 1998
       
    This study of 124 patients with diffuse intermediate/high-grade non-Hodgkin’s lymphoma, stage II bulky, III & IV received etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [VACOP-B], with cisplatin, cytarabine, and dexamethasone as a salvage regimen and other arm received VACOP-B plus high dose therapy and autologous bone marrow transplantation.
         
    There was no difference in remission rates; overall survival and disease free survival between the two groups. In a subset of patients according to the international Prognostic Index, patients with intermediate high risk and high risk disease did have a significant improvement in disease free survival with the use of high dose therapy over standard chemotherapy. However, no significant difference in overall survival was noted.
          

  • Deeg HJ, Leisenring W, Storb R, et al [Fred Hutchinson Cancer Research Ctr, Seattle; Univ of Washington, Seattle]
    Long-Term Outcome After Marrow Transplantation for Severe Aplastic Anemia
    Blood 91: 3637-3645, 1998
       
    The retrospective review of 212 patients who underwent marrow transplantation for aplastic anemia at the Fred. Hutchinson Cancer Research Center and survival for more than 2 years underwent assessment for long term mobidity and mortality. The presence of chronic graft versus host disease predicted a lower 20 year survival and a lower performance status. It was also associated with chronic skin problems, pulmonary problem, and depression. Other long-term complications due to sterioids, included cataracts, aseptic necrosis of the bone. 
      
    Fertility was maintained in large number of these survivors.
         

  • Ratanatharathorn V, Nash RA, Przepiorka D, et al [Univ of Michigan, Ann Arbor; Fred Hutchinson Cancer Research Ctr, Seattle; MD Anderson Cancer Ctr, Houston; et al]
    Phase III Study Comparing Methotrexate and Tacrolimus [Prograf, FK506] with Methotrexate and Cyclosporine for Graft-Versus-Host Disease Prophylaxis After HLA-Identical Sibling Bone Marrow Transplantation
    Blood 92: 2303-2314, 1998
       
    Acute GVHD occurs in 40% to 50% of allogeneic bone marrow transplantation recipient. This phase III, open-label, randomized, multicenter study assigned 165 patients to tacrolimus + methotrexate and 164 patients to methotrexate + cyclosporine for GVHD prophylaxis after histocompatibility leukocyte antigen-identical sibling marrow transplantation in patients with hematologic malignancy. 
      
    The incidence of grade II through IV GVHD was significantly lower in tacrolimus than in cyclosporine recipients despite this reduction in grade II & IV GVHD the patient receiving tacrolimus had a significantly worse overall survival and disease free survival than clyclosporine recipients. This was attributed to regimen related 
    toxicities especially in patients with advanced disease status. The editor comments further studies are warranted, particularly in patients with advanced disease before this becomes the standard GVHD prophylaxis regimen.
         

  • Hansen JA, Gooley TA, Martin PJ, et al [ Fred Hutchinson Cancer Research Ctr, Seattle; Veterans Affairs Med Ctr, Seattle; Univ of Washington, Seattle]
    Bone Marrow Transplants From Unrelated Donors for Patients With Chronic Myeloid Leukemia
    N Engl J Med 338: 962-968, 1998
        
    Allogenic bone marrow transplantation remains the only curative therapy for patients with chronic myeloid leukemia. This study of 196 patients Philadelphia chromosome positive CML in chronic phase underwent marrow transplantation from unmatched unrelated donors and were monitored for a median of 5 years, 35% had acute graft versus host disease [grade III and IV ]. Factors affecting adversely the survival including one year or longer interval between diagnosis and transplantation, an HLA-DRB1 mismatch in a high body weight index and age exceeding to years. The prophylactic use of fluconazole and ganciclovir improved survival. Hence patients younger than 50 years undergoing transplant from HLA matched unrelated donor within one year of diagnosis have a 5 year survival estimate of 74%. These results compare with marrow transplantation from an HLA matched identical sibling.
         

  • Slavin S, Nagler A, Naparstek E, et al [Hadassah Univ Hosp, Jerusalem; Ichilov Hosp, Tel Aviv, Israel]
    Nonmyeloablative Stem Cell Transplantation and Cell Therapy as an Alternative to Conventional Bone Marrow Transplantation With Lethal Cytoreduction for the Treatment of Malignant and Nonmalignant Hematologic Disease
    Blood 91: 756-763, 1998
       
    The first step in preparation of allogenic blood or bone marrow transplantation is myeloablative conditioning however this is frequently associated with hazardous immediate and late complications. This study of 26 patients with standard indication for allogeneic BMT reviewed non myeloablative conditioning consisting of fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan was well tolerated.
      
    Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose cyclosporin as the only graft-vs.-host-disease [GVHD] prophylaxis produced stable transient mixed chimerism. Absolute neutrophil count of 0.5 x 109/L or greater were achieved within 10-32 days and platelet counts above 20 X 109/L within 35 days. 14 patients had no GVHD and 4 patients developed severe GVHD on discontinuation of cyclosporine resulting in death. The chimerism in these type of transplant is believed to protect the host from severe acute GVHD. This may be effectively revised with graded increments of donor lymphocyte infusions resulting in elimination of malignant or genetically abnormal progenitor cells of host origin.
      
    The minimal toxicity associated with this approach suggests that it may be applicable to a broader range of patients previously not eligible for allogeneic BMT.
         

  • Khouri IF, Keating M, Korbling M, et al [ Univ of Texas, Houston]
    Transplant-Lite: Induction of Graft-Versus-Malignancy Using Fludarabine-based Nonablative Chemotherapy and Allogeneic Blood Progenitor-Cell Transplantation as Treatment for Lymphoid Malignancies
    J Clin Oncol 16: 2817-2824c, 1998
       
    This study of 15 patients with chronic lymphocytic leukemia and lymphoma received treatment [average of three previous regimens] with fludarabine based regimen, as nonmyeloablative regimen to produce immunosuppression followed by allogeneic stem cells infusion from histocompatibility leukocyte antigen identical siblings. Prompt hematopoietic recovery occurred in all patients who had engraftment, 8 had complete remission and 3 had decreased tumor mass. Four patients received donor lymphocyte infusion to augment the graft -vs.-leukemia/lymphoma [GVL] effect & the clinical response observed. These results suggest that allogeneic nonmyeloablative transplantation allows engraftment and GVL against lymphoid malignancies is feasible. Patients with chemosensitive disease and low tumor burden may benefit from this approach.
        

  • Verdonck LF, Petersen EJ, Lokhorst HM, et al [ Univ Hosp Utrecht, The Netherlands]
    Donor Leukocyte Infusions for Recurrent Hematologic Malignancies After Allogeneic Bone Marrow Transplantation : Impact of Infused and Residual Donor T Cells
    Bone Marrow Transplant 22 :1057-1063, 1997
      
    Previous studies have shown that complete donor T-cell chimerism is needed for graft vs. leukemia effect patients with chronic myeloid leukemia and multiple myeloma who have relapses after bone marrow transplantation are likely to respond to donor leukocyte infusion [DLI] in patients with acute leukemia in full-blown relapse, tumor reduction is needed before DLI. Mixed T-cell chimeras respond as well as complete donor T-cell chimeras to DLI. The DLI can be associated with substantial toxicity, 22% mortality rate from GVHD in this study.
        

  • Milpied N, Gaillard F, Moreau P, et al [ Univ Hosp, Nantes, France]
    High-Dose Therapy with Stem Cell Transplantation for Mantle Cell Lymphoma : Results and Prognostic Factors, a Single Center Experience
    Bone Marrow Transplant 22: 645-650, 1998
      
    Mantle Cell Lymphoma [MCL] is diagnosed as discrete entity in the recent years. The median survival of patients with MCL is 40 months with conventional chemotherapy. In view of the poor prognosis, high dose chemotherapy with addition of stem cell transplantation has been studied in 16 patients with stage IV MCL and 12 with bone marrow involvement. At a median of 36 months, 15 patients were still alive and 11 had no evidence of disease progression, between 2 and 51 month, 7 patients’ disease progressed.
       
    Patients receiving total body irradiation as conditioning had a better 4 year overall and disease free survival. Patients with blastic histology did poor worse. 
       
    The editor comments that high dose chemotherapy although effective for patients with relapsed intermediate and high grade lymphomas is not the answer for patients with MCL.
          

  • Avash LJ, Elias A, Ibrahim J, et al [Harvard Med School, Boston; Wake Forest Univ, Winston-Salem, NC]
    High-Dose Multimodality Therapy with Autologous Stem-Cell Support for Stage IIIB Breast Carcinoma
    J Clin Oncol 16: 1000-1007, 1998
      
    Stage III locally advanced breast cancer is made up of a variety of tumor types.
      
    This study of 4 stage IIIA and 46 stage IIIB breast cancer patients underwent induction chemotherapy with doxorubicin 90mg/m2 with granulocyte colony-stimulating factor [G-CSF] followed by high dose cyclophosphamide, thiotepa and carboplatin  [CTCb] with peripheral blood progenitor cell [ PBPC] support, and autologous bone marrow transplantation [ABMT] and mastectomy plus local radiotherapy to some patients. Tamoxifen [10 mg] twice a day for ER or PR positive patients. At 30 months disease free survival rate is estimated at 64% . 32% experienced relapses mainly at distant site, at a median at 17 months from CTCb.
      
    The editor comments that the preliminary results from this trial are promising , however at this point it is difficult to compare the preliminary results from this trial to other more mature phase II trials.
           

 

 

 

By |2022-07-20T16:44:00+00:00July 20, 2022|Uncategorized|Comments Off on Clinical Bone Marrow Transplant

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