Hematology and cell therapy最新文献

High doses of cytotoxic drugs may impair stem cell collection. Failure in stem cell collection by bone marrow aspiration can be rescued by harvesting Peripheral Blood Stem Cell (PBSC) after a combination of chemotherapy and hematopoietic growth factor. We, therefore, retrospectively evaluated the possibility of collecting PBSC after chemotherapy and/or G-CSF administration in 12 patients with insufficient Granulocyte-macrophage colony-forming unit (CFU-GM) counts after bone marrow aspiration (all patients had previously received heavy chemotherapy for hematologic malignancies); median collection of CFU-GM/kg count was 2,9 x 10(4)/kg (range 0,4 to 8 x 10(4)/kg) whereas the minimal count required for autografting is 10 x 10(4)/kg. Median collections of CFU-GM from PBSC were 5,8 x 10(4)/kg. While the CFU-GM collected in PBSC was higher than after bone marrow aspiration, only 5 patients had enough PBSC for autografting. In another case, addition of cells collected from both PBSC and bone marrow aspiration yielded a sufficient number of CFU-GM to allow autografting. Therefore in this selected and small group of patients, failure in bone marrow aspiration does not seem to be predictive of a low PBSC collection but a long therapy free interval and use of G-CSF alone for PBSC mobilization could constitute a valuable alternative. Three patients had a successful short term hematologic reconstitution out of the four patients having had an autograft.

We have used fludarabine to treat 36 patients with various lymphoid malignancies, including 29 with chronic lymphocytic leukemia (CLL). All these patients were heavily pretreated, and FAMP was prescribed on a compassionate basis. Eight patients (22%) developed severe autoimmune hemolytic anemia (AIHA) during or after treatment, and one died. Five patients had no previous history of hemolysis. These cases confirm the high incidence of AIHA after FAMP and suggest that the use of highly effective lymphocytotoxic agents such as fludarabine in heavily pretreated patients increases the risk of AIHA in CLL and other lymphoproliferative disorders.

The usual features of non-Hodgkin lymphomas (NHL) of the mucosa-associated lymphoid tissue (MALT) include monocytoid B-cell proliferation, and chronic inflammatory precursor lesions. Despite a reputation of being indolent, NHL of the MALT may disseminate to other MALT areas, and raise difficult therapeutic questions. We report a case of gastric NHL of the MALT whose evolution, despite an initial surgical treatment considered radical, was noticeable for a well documented breast relapse.

A review of the biomedical literature suggests that lymphocyte and neutrophil counts are probably the only blood cell count parameters whose independent pre-therapeutic prognostic values are significantly documented in lung cancer (and only in non small cell lung cancer). The independent pre-therapeutic prognostic value of these two parameters remains quite controversial however, and further studies should be conducted, and in particular, comparisons between neutrophils, lymphocytes, and serum cyfra 21-1. For the therapeutic follow-up, further prognostic evaluation studies are also necessary for blood cell count parameters as well as for serum cyfra 21-1. Clinical biologists still have to convince clinicians and/or journal editors that it is not scientifically acceptable for publications to omit detailing the analytical and pre-analytical methodologies used for blood cell count measurements.

Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is an aggressive form of acute leukemia that represents about one third of all adult ALL. Between 1984 and 1996, forty-three cases of Ph+ ALL (22 males and 21 females) were diagnosed in our institution by successful cytogenetic studies and/or molecular biology. Median age was 42 years (range, 20-71 years) with 28 patients aged below 50 years. Median leukocyte count was 39.7 x 10(9)/l on admission. Tumoral syndrome was seen only in 21 patients (49%) of which 4 cases presented with central nervous system (CNS) involvement. Among the 38 patients classified according to the French-American-British (FAB) criteria, 26 showed L1 and 9 L2 morphology. Three patients showed undifferentiated leukemia. Immunological study at diagnosis only showed B-cell lineage ALL with 95% of patients expressing CD10 and 50% expressing CD20. The Ph+ as sole anomaly was seen in 13 patients (31%), while additional chromosome changes were observed in 28 cases. Two patients were diagnosed only on molecular biology showing a Bcr/Abl rearrangement. Thirty-nine patients treated according to LALA protocols were eligible for the analysis of treatment outcome. Complete remission (CR) was achieved in 25 cases (64%, 95% CI: 47-79%). The median disease-free survival (DFS) and the median overall survival were 6 and 9 months respectively. Relapse was observed in 16 cases (64% of patients achieving CR). Initial parameters associated with a statistically significant worse prognosis were "blastic" fever, hyperuricemia, the presence of an extra Ph chromosome and patients whose marrow does not contain any normal mitosis (AA cases). As post-induction therapy, 13 cases followed a chemotherapy program (group 1) while 11 received early bone marrow (BM) or peripheral stem cell (PSC) transplantation (group 2) (5 allogeneic BM transplantation and 6 autologous BM or PSC transplantation). One patient did not receive any post-induction therapy. In group 1, the median DFS and overall survival were of 5 and 11 months respectively, while they were of 9 months and not reached respectively in group 2 with a 2-year survival rate of 51% (95% CI: 21-83%) confirming the requirement for intensified therapy in Ph+ ALL.

Severe disseminated intravascular coagulation (DIC) is a rare event in childhood. We report here a young body with a devastating DIC unresponsive to heparin, fresh frozen plasma and platelet support. This prompted the use of antithrombin III and protein C concentrates and the effects of this combination were temporarily spectacular. We suggest that the simultaneous administration of two inhibitors of blood coagulation could be of interest and should be evaluated in appropriate trials for the treatment of a devastating coagulopathy.

A great amount of scientific information, accumulated over recent years on the biology of Multiple Myeloma (MM), has fuelled speculation about the origin of malignant plasma cells, about a purported critical role played by the bone marrow stroma, and further still, on cytokine interactions and in particular that of IL-6 and its relationship with the immune system. Among the growth factors secreted by stroma cells, IL-6 is a potent stimulator of myeloma cells in vitro but does not induce a malignant phenotype in normal plasma cells. Many efforts have been produced to identify the stem cell in MM and probably memory B lymphocytes are the best candidates. The demonstration of a Graft vs Myeloma effect in the allogeneic setting strongly supports the immunotherapy in MM. Recent data also suggest that a virus (Kaposi-associated herpes virus, HHV-8) may be significantly associated with the development of MM. In parallel, progress has been achieved in the treatment of this incurable disease with well defined prognostic factors, more efficient supportive care and its corollary, improved quality of life and dose-intensified chemo-radiotherapy followed by autologous hematopoietic stem cell support. Improving the quality of grafts with the selection of CD34 positive cells is another approach aimed at reducing plasma cell contamination without impairing haematological recovery. An EBMT randomized study assessing the role of CD34 selection has been initiated by our group Increasingly efficient first-line therapy, better quality autografts and improved post-remission treatment with, for example, anti-idiopathic vaccination are the most promising future directions.

The impact on occult leukemia of GM-CSF as a sensitizing agent has not been studied. We treated 41 adult patients with de novo acute myeloid leukemia, 25 of whom achieved complete remission and were given 1 to 3 post-remission courses, each course including GM-CSF begun 4 days prior to chemotherapy and given until day 3. After a median follow-up of 32 months, the probability of remaining in continuous complete remission was 17% at 46 months. GM-CSF in this setting was not associated with an improved outcome, arguing against a priming effect.

A 61-year-old heart transplant recipient with parvovirus B19 infection, presented as a severe pure red cell aplasia (PRCA) with hemoglobin level of 5 g/dl. Both blood and bone marrow cells were positive for parvovirus B19 DNA, whereas specific immunoglobulins IgG and IgM were not informative. Bone marrow smears revealed erythroid hypoplasia without giant pronormoblasts. Autologous and allogenic bone-marrow cultures revealed a high inhibition by patient's serum on BFU-E growth whereas the number of CFU-GM were normal. Spontaneous remission of the anemia was observed despite the persistence of severe immunodeficiency as demonstrated by development of a monoclonal EBV lymphoproliferative disorder two months later. The "recovery" serum reversed the initial serum BFU-E inhibiting property. This case pinpointed the usefulness of blood or marrow cultures in parvovirus B19 infection of immunocompromised patients without normal Ig responses, as in other PRCA. Further, it argues that the usual immunoglobulin therapy may not be necessary in order to obtain a viral clearance.