Endre Kelemen

Multiple myeloma in pregnancy

This is a report on pregnancy complicated by multiple myeloma. Severe refractory anemia was present throughout the pregnancy and multiple myeloma was diagnosed in the second trimester. The anemia ceased after delivery but recurred one year later along with other signs of disease progression. The infant remained healthy after a 2‐year follow‐up.

Pregnancy in idiopathic aplastic anemia (report of 10 patients)

This paper reports on 6 patients with severe, 2 with moderate and 2 with mild aplastic anemia who had a total of 18 pregnancies after the diagnosis. All four pregnancies that occurred during the active state of severe and moderate aplastic anemias were electively terminated. Two out of 14 pregnancies that occurred during the long-term remission were electively terminated for non-medical reason, two spontaneous abortions occurred and 10 live births were seen. All offspring were healthy at follow-up. During pregnancy the circulating blood cell levels decreased in 1 out of 6 pregnancies in patients who were in remission from mild and moderate aplastic anemias, and in 4 out of 8 pregnancies in patients who were in remission from severe aplastic anemia. In all 5 cases that showed a relapse during pregnancy the remission recurred following the termination of pregnancy. The data presented suggest that aplastic anemia in long-term remission can unpredictably relapse during pregnancy, but its final outcome appears not to be affected by pregnancy. Furthermore, there is no correlation between the pre-pregnancy clinical course and the events during pregnancy. The outcome of pregnancy during the remission of aplastic anemia seems beneficial, and spontaneous delivery should be preferred.

Remarkably Reduced Transplant-Related Complications by Dibromomannitol Non-Myeloablative Conditioning before Allogeneic Bone Marrow Transplantation in Chronic Myeloid Leukemia

A non-myeloablative conditioning protocol containing dibromomannitol (DBM/cytosine arabinoside/cyclophosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from sibling donors. Risk factors include: accelerated phase (10 patients), older age (17 patients over >40 years) and long interval between diagnosis and BMT (27 months on average). Severe mucositis did not occur. Venoocclusive liver disease was absent. Infectious complications were rare. Although grade II–IV acute graft-versus-host disease (GVHD) was present in 9 (25%) cases, there were only 2 serious (III–IV) ones. Chronic GVHD occurred in 25 (69%) cases, preceded by acute GVHD in 9 of the 25 affected patients. Early hematological relapse, 7–29 weeks after BMT, developed in 6 patients (17.6%). No relapse was noted in the completely chimeric patients, however molecular genetic residual disease was observed in 6 patients, in most of them after transient short-term mixed chimeric state. Overall actual survival rate is 83.3% for the 36 cases, and leukemia-free survival is 72.2% for the 34 engrafted patients.

Immunological importance of chimerism in transplantation: new conditioning protocol in BMT and the development of chimeric state

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisits to induce chimerism are immuno-suppression, myeloablation, or severe immunodeficiency of the recipients on the one side and donor originated immuno-hematopoietic cells in the graft on the other. The pathologic or special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion, and various kinds of solid organ grafting. Different types of chimerism are known including complete, mixed and mosaic, or split chimerism. There are various methods used to detect the type of chimera state, depending on the immunogenetic differences between the donor and recipient. The induction of complete or mixed chimerism is first determinated by the effect of myeloablative therapy. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of GVHD, and the rate of relapse. However, the most important contribution of the chimeric state is in development of graft versus leukemia effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.

Chronic Idiopathic Myelofibrosis. A Reversible Disease

A patient with chronic idiopathic myelofibrosis was subjected to splenectomy 1 year after diagnosis. As a clinically unexpected finding, lymph node biopsy suggested the presence of non-Hodgkin lymphoma. The patient was subjected to intensive combined cytostatic therapy. In the following months, signs and symptoms of myelofibrosis regressed remarkably. The patient died 31 months after splenectomy in massive gastrointestinal bleeding. At post-mortem, myelofibrosis could not be detected in three bone marrow areas and a regular, fat-containing, hypercellular marrow was present. The nature of the previous lymph noede pathology was reconsidered, and angioimmunoblastic lymphadenopathy was diagnosed.

Granulocyte alkaline phosphatase activity: a measure of the emergence time of mature marrow neutrophils?

Early release of mature bone marrow granulocytes either with ‘empty’ stores or with exaggerated turnover rate of the marrow store furnishes more alkaline phosphatase positive neutrophils, whereas rele

Bone marrow transplantation in accelerated chronic granulocytic leukaemia using dibromomannitol-preconditioning instead of total-body irradiation

In a preliminary study on five patients with accelerated CGL, transplantation of allogeneic matched bone marrow was shown to be feasible without whole-body irradiation. Animal experiments and studies with cells cultured in vitro suggest that the cytocastic drug used to kill leukaemic clones (Myelobromol-Chinoin) does not injure haemopoietic stroma. The administration of this protocol is cheap and easy. Our preconditioning does not, in itself, eradicate the malignant CGL clone immediately: 15-20% of marrow mitoses were Ph1+ one month after transplantation. For this reason, additional cytostatic therapy was given in the course of the 3rd to 6th post-transplant months. No Ph1+ cells were observed from the fourth post-transplant month onwards. Very few severe acute complications were seen and two out of three matched transplanted patients are disease-free 27 + and 13 + months later. On the basis of the developing normal spleen architecture and the changing pattern of circulating NAP score values, particularly the months-long persistence of distinctly low scores, and then the delayed emergence of normal levels, we put forward a hypothesis, emphasizing the role of environmental factors, including the formation of a normal haemopoietic stroma in the successfully transplanted CGL patient.

Organ-Bound Hemopoiesis

Section 3.1 deals with the liver as hemopoietic organ and shows sections and smears of the various cell types found at different stages of development, with particular emphasis on morphological cell detail and the relationship between the hemopoietic cells and the parenchyma of the liver. The most interesting Stage of development is the initial phase of hemopoiesis; therefore a great part of the pictures are devoted to the study of the liver hemopoiesis during the early stages of development.

Intravascular Hemopoietic Cells

Chapter 2 examines the types of cells that can be detected in the circulating blood during embryonic and fetal development. As pointed out in the introduction, there is sufficient evidence to assume that all sites of intraembryonic blood cell formation commence their productive activity after undifferentiated precursor cells have migrated into these sites to initiate hemopoiesis. The blood acts as the major avenue for the migration streams of hemopoietic cells between the different sites of blood cell formation. Therefore, it is of interest to analyze the cell types Seen in the blood vessels of extraembryonic, embryonic, and fetal tissue at different stages of development.

Pregnancy in aplastic anemia treated with fetal liver and bone marrow hemopoietic cells and antithymocyte globulin

SummaryThis report describes a patient who had severe refractory anemia and thrombocytopenia during her first pregnancy. She had a remission after delivery but two years later aplastic anemia refractory to steroid and splenectomy developed. After treatment with steroids and antithymocyte globulin the patient had repeated infusions of hemopoietic cells derived from fetal liver and bone marrow, leading to a 7-year remission during which time she had a further successful pregnancy. The patient had a relapse one year later.