E. Neumann

Cell lineage heterogeneity in blast crisis of chronic myeloid leukaemia

Summary Blast cells from 45 patients with chronic myeloid leukaemia in blast crisis (CML‐BC) were immunologically phenotyped with a panel of 26 monoclonal antibodies and studied for terminal deoxynucleotidyl transferase (TdT) content. Out of 45 blast‐populations, 28 showed a myeloid, 14 a lymphoid, two a mixed and one an unclassifiable marker profile.

Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes

SummaryPluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n=3; RA with ring sideroblasts (RARS), n=3; RA with excess of blasts (RAEB), n=8; RA with excess of blasts in transformation (RAEBt), n=7; chronic myelomonocytic leukemia (CMML), n=2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.

Myeloid progenitor cells in the peripheral blood of patients with hairy cell leukemia and other leukemic lymphoproliferative disorders

We assayed granulocyte-macrophage committed progenitor cells (CFU-GM), erythroid committed progenitor cells (BFU-E) and pluripotent hemopoietic progenitor cells (CFU-MIX) in the peripheral blood of patients with hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). In 8 HCL patients retaining their spleens, the number of circulating CFU-GM, BFU-E and CFU-MIX were under the lower limits of normal controls in 6, 6 and 5 cases, respectively, and were in the lower normal ranges in the remaining cases. Six splenectomized HCL patients had generally more circulating progenitor cells than their nonsplenectomized counterparts. In the peripheral blood of 2 patients with ALL and 3 patients with CLL, progenitor cells of all types were markedly increased compared to their respective values in the blood of control subjects. Hairy cells from 2 HCL patients failed to inhibit CFU-GM, BFU-E and CFU-MIX derived colony growth from control peripheral blood mononuclear cells. In 3 HCL patients previously low circulating progenitor cells did not rise 5-7 months after RC-alpha 2-IFN treatment despite normalization of peripheral blood counts. Our results suggest that a reduction of the committed and pluripotent progenitor cell compartment might be at least in part responsible for the pancytopenia in the majority of patients with HCL.

Treatment of Severe Aplastic Anemia with Combined Immunosuppression (Antithymocyte Globulin and High-Dose Methylprednisolone)

Fifteen patients with transfusion-dependent severe aplastic anemia (SAA) were treated with combined immunosuppression consisting of horse-antithymocyte globulin (ATG; Atgam, Upjohn) and high-dose 6-methylprednisolone (MP). Oxymetholone was scheduled for 2 years but was discontinued in 7 patients after 10-385 days due to liver toxicity. Serious side effects usually seen in ATG monotherapy were rare during combined immunosuppression. Currently 12 of 15 patients are alive 110-1,275 days (median 475.5) after start of treatment. One patient has received too short treatment to be evaluated. All the others are transfusion-independent. Three patients died; two from septicemia before hemopoietic recovery could be expected and one after relapse. Our results confirm that the addition of high-dose MP abrogates the side effects of ATG monotherapy, and the addition of MP does not counteract, but rather enhances the beneficial effect of ATG in SAA. We recommend combined immunosuppressive treatment with ATG and high-dose MP as a highly feasible, safe and effectful therapy for patients with transfusion-dependent SAA.

High efficacy of the German multicenter ALL (GMALL) protocol for treatment of adult acute lymphoblastic leukemia (ALL) — a single-institution study

SummarySixty-one consecutive patients with acute lymphoblastic leukemia (ALL) (B-ALL excluded) were treated with the protocol described by Hoelzer et al. [15]. The complete remission (CR) rate was 85% (52/61 patients). Three patients died during induction therapy; six patients were refractory to treatment. The median duration of continuous complete remission (CCR), disease-free survival (DFS), and overall survival was 41.5, 41.4, and 40.8 months, respectively. At 5 years the probability of CCR was 49%, of DFS 43.5%, and of overall survival 41.6%. In the univariate analysis older age (>35 years,p=0.01), bcr-abl positivity (p=0.007), and time to CR (>4 weeks,p=0.05) were significantly unfavorable prognostic factors. In the multivariate analysis only age (p=0.006) and time to CR (p = 0.02) remained significant. Thus, our data confirm the high efficacy of this treatment regimen with regard to CR rate and remission duration.

Malignant histiocytosis with unusual features. Disseminated intravascular coagulation with severe hyperfibrinolysis, acute polyneuroradiculitis Guillain‐Barré, and a unique chromosome abnormality

The case of a 25‐year‐old man with the characteristic features of malignant histiocytosis (proliferation of abnormal histiocytic cells with erythrophagocytosis, hepatosplenomegaly, increased serum acid phosphatase, hypercalcemia, and bone pain) is reported. Chromosome studies revealed a near tetraploid karyotype with a pair of marker chromosomes. A few hours after initiation of chemotherapy with cyclophosphamide, Adriamycin (doxorubicin), vincristine, and prednisolone (CHOP regimen), the patient developed an acute ascending paralysis. Cerebrospinal fluid (CSF) findings were consistent with a diagnosis of Guillain‐Barré Syndrome. On the next day, disseminated intravascular coagulation (DIC) with severe hyperfibrinolysis occurred. After intensive chemotherapy, complete remission could be achieved.

In vitro culture studies of granulocyte/macrophage and erythroid progenitor cells in lymphoproliferative disorders

SummaryGranulocyte/macrophage progenitor cells (CFU-GM) and erythroid progenitor cells (BFU-E) have been assayed in peripheral blood (PB) and/or bone marrow (BM) from 12 patients with acute lymphocytic leukemia (ALL), 16 patients with chronic lymphocytic leukemia (CLL) and 31 patients with various forms of non-Hodgkin lymphoma (NHL) without BM involvement. Progenitor cell growth in PB and BM from the NHL patients did not differ statistically from controls (p>0.1). CFU-GM and BFU-E per ml PB were markedly increased in ALL and CLL patients (p< 0.001) while CFU-GM and BFU-E per plated BM cells from these patients were severely depressed (p< 0.001). Lymphoblasts from one ALL patient failed to inhibit CFU-GM and BFU-E-derived colony growth from control PB mononuclear cells. The high levels of circulating progenitor cells in ALL and CLL patients clearly distinguish them from other cytopenic hematological malignancies, in which decreased progenitor cell levels have been demonstrated previously (acute myeloid leukemia, hairy cell leukemia). The cause of this finding and its pathophysiological implication still remains to be established.

Indium 111‐labeled platelet kinetic studies and platelet‐ associated igg in hairy cell leukemia

In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet‐associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous 111In‐labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 × 109/1; range, 80–190 × 109/1) as well as higher levels of PAIgG (x = 10.7%; range, 5.8–16.9%), than nonsplenectomized patients (platelets x = 76 × 109/1, range 40–100 X 109/1; PAIgG x = 3.2%, range 2.2–4.2%). A normal recovery of 111in‐labeled platelets was found in Splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50–82.5%, versus x = 22.4%, range, 15–28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of 111In‐labeled platelets in nonsplenectomized patients suggests “hypersplenism” with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune‐mediated platelet destruction. Cancer 58:234–237, 1986.

CHOP-firstline treatment in NHL with unfavorable prognosis — Evaluation of therapeutic response and factors influencing prognosis

Summary58 NHL-patients (9 large cell centrocytic, 18 centroblastic, 16 immunoblastic, 15 lymphoblastic lymphomas) were treated immediately after diagnosis with CHOP-chemotherapy regardless of the extent of disease. Because of the advanced age of the majority of patients (median age 61 years, range 22–85 years) a reduced dose in the first two cycles was administered. Statistically significant prognostic variables influencing survival were the following: histologic subtypes according to the Kiel-classification (p<0,05), B-symptoms (p<0,001), blood sedimentation rate (p<0,02) and LDH (p<0,0005). With regard to prognosis there was no difference between patients over 60 years of age and younger ones (p<0,4). Patients achieving complete remission survived significantly longer (p<0,0001). Ann Arbor stages were of limited value, since patients with CS II disease and accumulation of risk factors (B-symptoms, abdominal disease, bulky tumor masses) showed a poorer outcome than patients with CS III who did not have these risk factors. A risk factor score summarizing features influencing prognosis is described and might be a useful tool in stratifying the heterogenous group of NHL with unfavorable prognosis.

Survival and Quality of Life in 23 Patients with Severe Aplastic Anemia Treated with Bone Marrow Transplantation (BMT)

SummarySurvival and quality of life are reported in 23 pretransfused patients with severe aplastic anemia (SAA) who underwent bone marrow transplantation (BMT). The projected survival is 76% with 18 of 23 patients being alive 332 to 1677 days post graft (median: 842). 5 patients died between day 4 and 416. 12 of 17 patients at risk developed chronic graft versus host disease (GVH-D). 4 of these patients have a diminished quality of life due GVH-D related disabling manifestations. Autologous haemopoietic recovery was excluded in all patients by the demonstration of haemopoietic chimerism. We recommand age-adapted rejection prophylaxis; such strategy may help to diminish disabling graft versus host disease in otherwise haematologically reconstituted survivors.