Wolfram Ebell

After major ABO‐mismatched allogeneic hematopoietic progenitor cell transplantation, erythroid engraftment occurs later in patients with donor blood group A than donor blood group B

BACKGROUND: Isohemagglutinins directed against the donor blood group frequently delay erythroid engraftment after major ABO‐mismatched allogeneic hematopoietic progenitor cell transplantation (HPCT). Graft‐versus‐host reactions are capable of accelerating the clearance of isohemagglutinins. Whether immunogenicity of the A‐ and B‐antigen is important in this process is unknown.

Allogeneic Bone Marrow Transplantation in Childhood Leukemia: Results and Strategies in the Federal Republic of Germany

The treatment of acute leukemias in child-hood has been very successful in the Federal Republic of Germany. Multicenter trials for both, acute lymphoblastic leukemia (ALL) and acute nonlymphoblastic leukemia (AML), have existed for more than 10 years now and since about 1980 almost 90% of children have been treated within the two BFM trials [1, 2] or the COALL trial [3]. Intensive induction therapy has led to results which belong to the best cure rates so far achieved in these childhood malignancies. An overall disease-free survival of 70% for ALL and at least 50% for AML has been documented. For ALL, conventional chemotherapy is able to cure even a distinct part of those children where late relapses occur (gt;1/2 year after the end of maintenance therapy). This is not true, however, for children suffering from ALL with early relapses and those with AML for whom the outcome of therapy following a relapse is very unfavorable.

Die Transplantation hämatopoetischer Stammzellen@@@The transplantation of hematopoietic stem cells. Part II: Indications after myeloablative therapy: Teil II: Indikationen zur Transplantation von hämatopoetischen Stammzellen nach myeloablativer Therapie

Zusammenfassung□ Hämatopoetische Stammzellen werden bei malignen Erkrankungen transplantiert, um nach knochenmarkzerstörender (myeloablativer) Ganzkörperbestrahlung oder Chemotherapie die Blutbildung und das Immunsystem zu ersetzen oder wiederherzustellen. Bei Erkrankungen des Knochenmarks oder der Lymphopoese substituieren allogene Stammzellen die defekten Zellen. Mit dieser Therapie liegt bei akuten Leukämien die Chance der Krankheitsfreiheit nach fünf bis acht Jahren bei 50 bis 80%. Der allogene Graft-versus-Leukämie-Effekt durch immunreaktive Zellen reduziert bei myeloischen und lymphoiden Neoplasien die Rezidivrate. Bei chronischer myeloischer Leukämie überleben 40 bis 70% der Patienten krankheitsfrei nach mehr als fünf Jahren. Bei malignen Lymphomen wird die autologe Stammzelltransplantation bevorzugt, die bei 40 bis 60% der Patienten eine Heilungschance bietet, welche auch bei allogener Transplantation wegen einer höheren Komplikationsrate nicht höher liegt. Es werden zunehmend auch Patienten ohne Heilungsaussicht behandelt, bei denen jedoch die Krankheitsprogredienz signifikant verzögert und die Überlebenszeit verlängert wird. Dies gilt für die myeloablative Therapie mit autologer Transplantation bei chronischer myeloischer Leukämie, multiplem Myelom und bestimmten soliden Tumoren. Es zeichnet sich ab, daß Patientinnen mit Mammakarzinom und axillären Lymphknotenmetastasen von einer adjuvanten hochdosierten Chemotherapie mit autologer Stammzelltransplantation profitieren: krankheitsfreies Überleben ohne Hochdosistherapie 30%, mit Hochdosistherapie und Transplantation > 60%. Bei angeborenen Stoffwechselkrankheiten werden fehlende Enzyme mit den transplantierten allogenen Zellen substituiert. Das Verfahren wird auch bei Autoimmunkrankheiten sowie bei der Gentherapie mit transfizierten hämatopoetischen Stammzellen in klinischen Forschungsprojekten eingesetzt.Summary□ The destruction of hematopoiesis and lympopoiesis by total body irradiation or high dose chemotherapy for the treatment of malignancy can be reversed by the transplantation of allogeneic or autologous hematopoietic stem cells. In primary disorders of bone marrow or immune system, allogeneic stem cells replace deficient cells. Acute leukemias can be cured, with in 50 to 80% disease free survival after 5 to 8 years. The allogeneic graft versus leukemia effect by immunoreactive cells reduces the relapse rate in myeloid and lymphoid malignancies. 40 to 70% of patients with chronic myeloid leukemia remain disease free after more than 5 years. Patients with malignant lymphoma have a 40 to 70% chance of cure with autologous transplantation, which is not increased by allogeneic cells, because of a higher incidence of severe complications. An increasing number of patients without option for cure is treated with the aim of prolonging remission or retarding disease progression, such as in chronic myeloid leukemia, multiple myeloma and certain solid tumors. New studies suggest in breast cancer with axillary lymph node metastases, that adjuvant high dose chemotherapy with autologous stem cell support will significantly improve disease free survival from 30 to over 60% after 3 to 5 years. In congenital metabolic and storage diseases deficient enzymes are substituted by the allogeneic cells. Clinical trials explore the use of stem cell transplantation after myeloablative therapy in autoimmune disorders as well as in gene therapy with transfected hematopoietic stem cells.The destruction of hematopoiesis and lymphopoiesis by total body irradiation or high dose chemotherapy for the treatment of malignancy can be reversed by the transplantation of allogeneic or autologous hematopoietic stem cells. In primary disorders of bone marrow or immune system, allogeneic stem cells replace deficient cells. Acute leukemias can be cured, with in 50 to 80% disease free survival after 5 to 8 years. The allogeneic graft versus leukemia effect by immunoreactive cells reduces the relapse rate in myeloid and lymphoid malignancies. 40 to 70% of patients with chronic myeloid leukemia remain disease free after more than 5 years. Patients with malignant lymphoma have a 40 to 70% chance of cure with autologous transplantation, which is not increased by allogeneic cells, because of a higher incidence of severe complications. An increasing number of patients without option for cure is treated with the aim of prolonging remission or retarding disease progression, such as in chronic myeloid leukemia, multiple myeloma and certain solid tumors. New studies suggest in breast cancer with axillary lymph node metastases, that adjuvant high dose chemotherapy with autologous stem cell support will significantly improve disease free survival from 30 to over 60% after 3 to 5 years. In congenital metabolic and storage diseases deficient enzymes are substituted by the allogeneic cells. Clinical trials explore the use of stem cell transplantation after myeloablative therapy in autoimmune disorders as well as in gene therapy with transfected hematopoietic stem cells.