Autologous and allogeneic bone marrow transplantation in acute myeloid leukemia in first complete remission: an update of the Genoa experience with 159 patients

Summary In the attempt to evaluate the role of Autologous and Allogeneic Bone Marrow Transplantation, we have retrospectively analyzed 159 patients with Acute Myeloid Leukemia in first complete remission treated in our Unit, most of whom were referred from other Institutions. High-dose therapy was uniform and consisted of cyclophosphamide 60 mg/kg/d on two consecutive days and TBI in a single dose (10 Gy) for ABMT patients and in fractionated doses (3.3 Gy × 3 days) for BMT patients. Eight years actuarial survival was similar in two groups (52% for BMT and 49% for ABMT). The actuarial risk of relapse for BMT and ABMT was 29% and 43%, respectively. Considering that none of ABMT patients was purged with in vitro technique, this review seems to confirm the importance of in vivo purging with postremission intensification, immediately before the harvesting. Of course, more patients and a longer follow-up are needed to drow final conclusions.     

Transplantation of peripheral blood progenitor cells from HLA-identical sibling donors

Transplantation of peripheral blood progenitor cells (PBPCs) has largely replaced autologous bone marrow transplantation. The same might occur in the allogeneic setting if the favourable initial experience with allogeneic PBPCT is confirmed. We analysed all primary transplants utilizing unmodified PBPC from HLA-identical sibling donors reported to the European Group for Blood and Marrow Transplantation (EBMT) for 1994. 59 patients with a median age of 39 years received myeloablative therapy for acute myelogenous leukaemia (23 patients), acute lymphoblastic leukaemia (13), chronic myelogenous leukaemia (nine), lymphoma (seven), or other diagnoses (seven) mostly of advanced stages followed by transplantation of allogeneic PBPC. Three patients died soon after grafting, the others showed prompt haemopoietic recovery with median times to recover an absolute neutrophil count (ANC) above 0.5 and 1.0×10⁹/l of 15 (range 9–27) and 17 d (range 10–28) respectively. Time to platelet recovery above 20 or 50×10⁹/l was 16 (range 9–76) and 18 d (range 12–100) respectively. 27 patients (46%) developed no or mild acute graft-versus-host disease (GVHD). The incidence of moderate (grade II) disease was 27%; 24% of the patients developed severe acute GVHD (grades III or IV). 55% of patients who were alive 90 d after transplantation developed chronic GVHD, the probability to develop extensive chronic GVHD was 32% (95% confidence interval 22–42) with a median follow-up of 14 months. Overall and event-free survival (EFS) at 1 year were 54% (CI 48–60) and 50% (CI 43–57), respectively, the relapse incidence was 23% (CI 17–29). EFS was 67% (CI 55–79) in patients transplanted for acute leukaemias in first complete remission, chronic myelogenous leukaemia in first chronic phase, or severe aplastic anaemia. Transplantation of allogeneic PBPC resulted in prompt and durable engraftment. The incidence and severity of acute and chronic GVHD seemed comparable to that observed after allogeneic BMT. Overall and event-free survival in this cohort of patients, most of whom suffered from advanced leukaemia or lymphoma, is encouraging, suggesting that the high numbers of T lymphocytes and/or natural killer cells contained in a typical PBPC collection product exert a vigorous graft-versus-leukaemia effect. Further evaluation of allogeneic PBPCT is highly desirable.     

A to O Bone Marrow Transplantation in Severe Aplastic Anaemia: Dynamics of Blood Group Conversion and Demonstration of Early Dyserythropoiesis in the Engrafted Marrow

A to O bone marrow transplantation was performed in a 25-year-old male affected with severe aplastic anaemia, the donor being an HLA compatible brother. Three plasma exchanges had to be performed with an Aminco separator to remove the original and recurring anti-A isohaemagglutinins. The dynamics of O to A blood group conversion were followed by means of differential agglutination. An early wave of marked dyserythropoiesis was observed in the engrafted marrow. Mild to moderate GvHD was treated successfully with MTX, bolus high dosage 6-methylprednisolone and, at relapse, with intravenous ALG.     

Lymphoid antigens (LY) on leukaemic cell populations: recognition by means of antilymphocytic globulins and clinical implications.

Cells obtained from 120 cases of acute and chronic leukaemias (both non-lymphocytic, ANL, and lymphoid leukaemias, ALL) were reacted in an indirect immunofluorescence test with antilymphocytic globulins (ALG) directed against different lymphoid cell populations (spleen, lymph node, tonsil, thymus, thoracic duct, peripheral blood lymphocytes, chronic lymphatic leukaemias cells and cultured lymphoblasts). The aim of this study was to recognize lymphoid antigens expressed on both thymus and bone marrow derived lymphocytes, as well as on leukaemic cells. Our 4 years' experience can be summarized as follows: (1) unabsorbed ALGs strongly react with B, T cells, as well as with all leukaemic cells tested; (2) myeloid cross-reactivity can be overcome after proper absorptions with cells from AML or AMoL or CML or with neutrophils from healthy donors; (4) MY-absorbed ALG can still interact with B, T lymphocytes, CLL-cells, blasts from B, T, null ALL and cells from CML in lymphoid blastic crisis, but not with myeloid or monocytic cells; (5) four out of five undifferentiated leukaemias proved to be reactive to ALG, as well as four out of 31 AML. All ALG-positive cases (LY⁺ cases), irrespective of their cytochemical diagnosis, were treated with vincristine-prednisone, with good response rates. The biological and clinical significance of these results are discussed.     

Reduced intensity conditioning with thiotepa, fludarabine, and melphalan is effective in advanced multiple myeloma

Fifty-three patients with multiple myeloma (MM) underwent an allogeneic stem cell transplant (HSCT) from their HLA identical siblings using a reduced-intensity conditioning consisting of thioteopa 5 mg/kg, fludarabine 90 mg/m(2), and melphalan 80 mg/m(2). Their median age was 52 years (range 38 - 68) and the interval from diagnosis 12 months. Forty-three patients (82%) had advanced disease and 33 had previously been treated with high-dose therapy with one (N = 21), or more (N = 12) autologus transplants. Ten (18%) had their allograft programmed after induction chemotherapy. The majority (N = 44) received peripheral blood as stem cell source. Acute graft-versus-host disease (GVHD) grade II - IV developed in 45%, but grade III - IV in only 5%. Cumulative incidence of chronic GVHD was 64%. Sixty-two per cent were in complete remission (CR) following transplantation. Transplant-related mortality was 13%. Relapse incidence was 32%. With a median follow-up of 22 months, 3-year overall survival is 45% and progression free survival (PFS) 37%. The thiotepa, fludarabine, and melphalan conditioning regimen can produce remissions in the majority of MM patients with a limited transplant mortality rate. When used as first line treatment the results of transplantation appear even more encouraging.     

Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin.

Immunosuppressive therapy has been shown to induce sustained hematological responses in a subset of patients with myelodysplastic syndromes (MDS). In particular, antithymocyte globulin (ATG), a polyclonal immunoglobulin induces hematological responses in up to 60% of MDS patients. We report herein on the results of a retrospective multicenter study on the use of ATG in the treatment of 96 patients with MDS. Patients were evaluated for duration of response to ATG, as well as survival after administration of ATG. The median age of the cohort was 54.7 years (range: 19-75 years), with a median follow-up of 33.8 months (range: 0.8-133 months). A total of 40 patients (42%) achieved a hematological response, of which 30 patients (75%) had a durable hematological response lasting a median duration of 31.5 months (range: 6-92 months). On multivariate analysis, both low International Prognostic Scoring System (IPSS) and bone marrow (BM) hypocellularity were independent predictive factors for improved response to ATG (IPSS Int-2/high: odds ratio (OR) 0.08, P=0.018 and BM normo/hypercellularity: OR 0.49, P=0.012). In addition, IPSS was the sole predictor of overall survival, with Int-2/high risk patients having a significantly poorer survival outcome (OR 0.08, P<0.01). In conclusion, this study identifies BM hypocellularity and a low IPSS as important factors predicting response to ATG.     

Persistence of a positive (1,3)-beta-D-glucan test after clearance of candidemia in hematopoietic stem cell transplant recipients

In 6 hematopoietic stem cell transplant (HSCT) recipients with candidemia, the (1,3)-β-d-glucan (BG) test was positive a median of 2.5 days after a positive blood culture. Only in 1 patient did BG positivity precede positive blood cultures. BG concentrations decreased in patients with clinical response, but positive BG results persisted long after blood cultures became sterile (median, 48 days).