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PubMed1991

Successful stimulation of autologous bone marrow recovery by GM-CSF and IL-3 after an unrelated donor BMT for juvenile CML complicated by graft failure.

We report the case of a boy with juvenile chronic myeloid leukemia (jCML), who after initial treatment with interferon alpha-2 (IFN) and hydroxyurea underwent bone marrow transplantation (BMT) from a matched unrelated donor complicated by graft failure. Subsequent stimulation of hematopoiesis by GM-CSF and IL-3 promoted autologous recovery. In contrast to the course of disease pre-BMT, the boy is now off any therapy remaining in complete remission more than 500 days after BMT.

Bone Marrow↗
PubMed1991

Blood cell kinetics after a 385 cGy total body irradiation given to a CML patient for bone marrow transplantation.

Fractionated total body irradiation was given to a patient with chronic myeloid leukemia as part of a conditioning regimen for bone marrow transplantation. The radiation treatment was discontinued after the third fraction (total dose: 385 cGy) and no bone marrow graft was given because of the patient's refusal. Peripheral blood lymphocyte levels were monitored for 3 months and lymphocyte subsets up to 50 days post-irradiation. Lymphocyte numbers reached the nadir 48 h after the last fraction and lymphopenia was still present 3 months later. All lymphocyte subsets (T, B, CD4 and CD8 cells) showed a similar decrease except for natural killer cells which exhibited a larger decline. The regenerative capacity of T cells, CD4 subset and natural killer cells was less than that of B cells and CD8 lymphocyte subsets.

Adult↗
PubMed1990

Prolonged suppression of myeloid progenitor cell numbers after stopping interferon treatment for CML may necessitate delay in harvesting marrow cells for autografting.

Fourteen patients with chronic myelogenous leukemia in chronic phase who had achieved hematological remission after alpha-interferon (IFN) therapy were evaluated for their ability to form hemopoietic colonies in vitro. Patients were studied both before and after discontinuation of IFN to assess the optimal timing for a further therapeutic approach consisting of stem cell collection followed by autologous bone marrow transplantation (ABMT). Before stopping IFN a profound inhibition of CFU-GM and BFU-E growth was observed. The numbers of CFU-GM and BFU-E in the bone marrow recovered to 50 per 2 x 10(5) cells plated at a median of 158 and 122 days, respectively, after stopping IFN. At that time, 12 patients were submitted to stem cell harvest and subsequently to ABMT. All patients showed complete engraftment and hematological reconstitution; cytogenetic improvement was observed in eight (67%) cases; two patients displayed complete disappearance of the Ph1 chromosome, confirmed at the molecular level. Eleven of the 12 patients are still in hematological remission at a median of 18 months from autografting and a median of 48 months from diagnosis.

Bone Marrow↗
PubMed1990

[Interactions of the phytopathogenic bacteria Erwinia with phage P1 CRL100 CML].

The bacteriophage P1 Cm clr100 lysogenises the bacteria E. chrysanthemi, E. aroideae, E. atroseptica being localized in the cytoplasm, replicating but causing no cell lysis. The prophage induction results in transformation of the lysogenic bacteria E. chrysanthemi into nonviable filamentous cells. However, a portion of cells gets rid of the prophage and gives rise to normal heritage inheritors permitting to use the bacteriophage as an efficient vehicle for introducing the transposons into the chromosome of E. chrysanthemi. The transposon Tn9 has been found to insert into the different chromosomal sites causing no inactivation of the genes, while the transposition of Tn5 from the bacteriophage P1::Tn5Cmclr100 induces the different mutations with the frequency up to 3%. The bacteriophage P1Cmclr100 may also serve a tool for construction of the homology regions in the chromosome of E. chrysanthemi and Flac+ plasmid for further construction of Hfr-type donors.

Bacteriophages↗
PubMed1990

The Philadelphia translocation in CML and ALL: recent investigations, new detection methods.

As a consequence of the Ph translocation, a bcr-abl fusion gene is formed that encodes chimeric bcr-abl proteins. The latter are probably causally involved in leukemogenesis, although the mechanism is not yet known. Meanwhile, the heterogeneous aspects of the Ph translocation have been explored in an effort to disclose their eventual clinical significance. Innovative and useful methods have been devised for the detection of the Ph translocation products e.g. the PCR technique or the production of specific antibodies that undoubtedly will prove to be of great help to patients and clinicians in future.

Chromosome Mapping↗
PubMed1990

Molecular analysis of a CML patient with a long duration of chronic phase before and after lymphoid blast crisis.

A patient who was diagnosed with chronic myeloid leukemia remained in chronic phase for 14 years before progressing into a lymphoid blast crisis in 1983. The acute phase was successfully treated, and the patient has remained in an indolent chronic phase to date. Cytogenetic and molecular analysis during this second chronic phase confirm the presence of the Philadelphia chromosome and its transcribed BCR-ABL mRNA. The breakpoint within M-bcr occurred in the 3' portion of the region and expressed a hybrid joining the b3 exon of BCR to the a2 exon of ABL.

Blast Crisis↗
PubMed1989

Cardiac arrhythmia in a CML patient treated with interferons.

We report a case of a 33-year-old woman who developed episodes of palpitation while receiving weekly alternating doses of daily intramuscular recombinant interferon alpha-2a (rIFN alpha-2a) and recombinant interferon gamma (rIFN gamma) for Philadelphia chromosome-positive chronic myelogenous leukemia. The electrocardiogram (ECG) and ambulatory Holter monitoring showed first-degree atrioventricular (A-V) block and episodes of junctional tachycardia. The ECG abnormality and palpitation disappeared after discontinuation of therapy. On rechallenge with recombinant interferon alpha-2b (rIFN alpha-2b) alone, there was recurrent palpitation and first-degree A-V block. Subsequent treatment with various doses of rIFN alpha-2b established a dose-response relationship between rIFN alpha-2b and palpitation in our patient. In view of increasing use of rIFNs in the clinical setting, this potential, albeit uncommon, toxicity requires attention and further investigation.

Adult↗