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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fourteen children between the ages of 2 and 5 years with juvenile chronic myelogenous leukemia were given cyclophosphamide, total-body irradiation, and marrow transplants. Unmodified marrow was given to six patients who received marrow from HLA-identical siblings and eight patients who received marrow from family members HLA identical for one haplotype but mismatched for one to three loci on the nonshared haplotype. Five patients died of transplant-related complications, and three relapsed at 48, 81, and 1,670 days posttransplant and died of leukemia. Six patients survive in continuous remission from 0.5 to 11.5 years posttransplant.
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PMID:Allogeneic marrow transplantation for children with juvenile chronic myelogenous leukemia. 328 22

Twelve children with juvenile chronic myeloid leukemia (JCML) received chemotherapy or bone marrow transplants. The median survival of the patients treated with myelosuppressive agents was 19 months. These results demonstrate that intensive chemotherapeutic and supportive measures can prolong survival in JCML but do not affect ultimate outcome. Purported differentiation inducers--low dose ara-C and 13-cis-retinoic acid--were not effective in two patients. Two patients were prepared for bone marrow transplantation with standard antileukemic cytoreduction regimens; one died very early post-transplant, and the other had early reemergence of his disease. The third transplant patient underwent transplantation after his disease had entered an accelerated phase. He received a different immunosuppressive pretransplant regimen, but the leukemia recurred. The latter two patients initially engrafted with mismatched T cell-depleted marrow grafts, but had recurrence of the disease. Our data suggest that marrow transplantation is possible for JCML patients without HLA-identical donors, but for successful marrow transplantation different measures are necessary to eradicate the abnormal stem cell compartment.
Leukemia 1987 Oct
PMID:Juvenile chronic myeloid leukemia: therapeutic insights. 331 35

A rare type of rapidly fatal childhood leukemia, generally called juvenile chronic myelogenous leukemia, is characterized by absence of the Philadelphia chromosome and a predominantly monocytic proliferation, among other features. Unlike Philadelphia chromosome positive chronic myelogenous leukemia, this disease is neither chronic nor principally a disorder of granulocytic cell lines. A case is presented, with several clinical and laboratory parameters useful in establishing the correct diagnosis, and a change in terminology to "rapidly progressive juvenile myelomonocytic leukemia" is proposed.
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PMID:Rapidly progressive myelomonocytic leukemia (juvenile CML). 347 55

At diagnosis peripheral blood (PB) or bone marrow from patients with juvenile chronic myelogenous leukemia (JCML) have shown two reproducible abnormalities when studied in cell culture: impaired growth of normal hematopoietic progenitors and excessive proliferation of malignant monocyte-macrophage elements. We used these findings to assess quality of treatment response by serially studying PB specimens from four JCML patients (patients 5, 7, 8, and 9) in complete chemotherapy-induced remission. PB readily yielded high numbers of monocyte-macrophage colonies in CFU-C and CFU-GEMM assays when cultured in early remission, and the colonies were cytogenetically proven to have arisen from a malignant clone in patient 9. When studied later in remission, the abnormal cell proliferation persisted in three of the four patients, but in patient 8 PB colony growth resembled controls. Similarly, when PB from patient 8 was studied in liquid culture without using added growth factor, cell proliferation declined identical to controls, whereas PB from the other three patients showed exuberant growth of monocyte-macrophage elements. Patient 8 successfully completed therapy and has been in a long-term, disease-free remission. The other three had recurrent, ultimately fatal disease. The cell cultures have allowed detection of residual abnormal cells that circulate in PB of JCML patients in remission. Although patient numbers were small because of the rarity of JCML, the data suggested that persistence of leukemia cells in these patients had a bearing on clinical outcome.
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PMID:Residual juvenile chronic myelogenous leukemia cells detected in peripheral blood during clinical remission. 347 1

We have studied by means of DNA-mediated gene transfer the activation of protooncogenes in human myeloid leukemias that represent various stages of myeloid differentiation. DNA from three cell lines, HL-60 (promyelocytic leukemia), Rc2a (myelomonocytic leukemia), and KG-1 (acute myeloblastic leukemia), was capable of transforming NIH/3T3 cells. Hybridization analysis indicated that, in all three tumor cell lines, the N-ras oncogene was activated. The cell lines U-937 ("histiocytic lymphoma") and K-562 (erythroblastic leukemia) yielded no transforming DNA. Fresh leukemia cells derived from an acute myelomonocytic leukemia patient and from a juvenile chronic myelogenous leukemia patient contained an activated N-ras and c-Ki-ras oncogene, respectively. DNA from some other myelogenous leukemia patients was not able to transform NIH/3T3 cells. Our results indicate that hematopoietic tumors of the myeloid lineage may contain oncogenes active in NIH/3T3 cell transformation and that, in particular, the N-ras oncogene may be activated in tumors representing various stages of maturation.
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PMID:Oncogene activation in human myeloid leukemia. 385 67

Myelodysplastic syndrome (MDS) in childhood is considered to be very rare, but sound epidemiologic data are lacking. We report a population-based study of MDS in Denmark from 1980 to 1991. The medical charts were reviewed of 988 children identified from the Danish National Hospital Discharge Registry with a diagnosis of myeloid leukemia or blood cytopenia. Blood and bone marrow smears from all cases of possible MDS were re-evaluated. The cases were categorized according to the FAB classification, with the exception of chronic myelomonocytic leukemia (CMML) in which more than 5% myeloblasts in the blood was accepted. Juvenile chronic myeloid leukemia (JCML) was included as CMML. MDS was diagnosed in 46 children representing 9% of all hematologic malignancies in children less than 15 years of age. The annual incidence was 4.0/million and did not increase with time. Refractory anemia with excess of blasts and CMML each accounted for one third of the cases. Down syndrome was present in seven children. Other predisposing conditions included Fanconi anemia, neurofibromatosis, constitutional trisomy 8 mosaicism, and familial leukemia. Only one child had therapy-related MDS. The study indicates that the incidence of childhood MDS is higher than generally assumed and approximate to the incidence of acute myeloid leukemia.
Leukemia 1995 Sep
PMID:Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. 765 25

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.
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PMID:Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia. 772 69

The leukemias of infancy, characterized by an equal distribution of lymphoid and myeloid subtypes, account for 2.5-5% of the acute lymphoblastic leukemias (ALL) and 6-14% of the acute myeloid leukemias (AML) of childhood. Rearrangements of the MLL gene on chromosome 11q23 are the most common genetic abnormalities in both ALL and AML, occurring in 70-80% and approximately 60% of cases, respectively. Infants with ALL and a rearrangement of MLL typically present with hyperleukocytosis, massive organomegaly, CNS involvement, CD10- B-lineage phenotype and myeloid-associated antigen (CD15) expression. Prognosis in these cases is uniformly poor, whereas in similar cases without the genetic defect, it is good to intermediate. The presenting features of infant AML include monoblastic or myelomonoblastic morphology, hyperleukocytosis and extramedullary involvement. Expected outcome approximates that for ALL (approximately 30% long-term survival rate). Rare congenital forms of lymphoid or myeloid leukemia, manifested at birth or during the first month of life, carry a dismal prognosis, especially when a MLL/11q23 rearrangement is present; such cases should be carefully distinguished by chromosomal/molecular analysis and cell culture techniques from transient myeloproliferative disorders which require only supportive care but close follow-up for subsequent development of leukemia. Juvenile chronic myeloid leukemia also can occur in infants and may be responsive to chemotherapy alone. Rapid progress has been made over the past decade in understanding the biology of infant leukemias. The biggest challenge now is to develop more effective treatment, especially for patients with MLL rearrangements.
Leukemia 1995 May
PMID:Biology and treatment of infant leukemias. 776 37

A pre-B acute lymphoblastic leukemia (ALL) cell line with monosomy 7 was established from a child with juvenile chronic myelogenous leukemia (JCML) in lymphoid blast crisis. Analysis of the growth properties of the cell line, termed 'W1' showed an interleukin-1 (IL-1) mediated autocrine pattern of cell proliferation with the following features: W1 colony growth without added growth factor was density-dependent and colony growth was augmented with serum-free autologous cell culture supernatant; exogenous IL-1 beta had a growth-promoting effect on W1 colony numbers when cells were seeded at low density; W1 cells constitutively expressed mRNA for IL-1 beta, and high levels of IL-1 beta were measured in W1 cell lysates; anti-IL-1 beta antibodies as well as IL-1 receptor antagonist markedly suppressed W1 colony growth when either was added to cultures of cells seeded without growth factors at low density; anti-GM-CSF antibodies and anti-IL-3 antibodies had no inhibitory effect on W1 colony growth. Whereas W1 colony growth was also augmented by adding IL-3, IL-4, IL-6, IL-7, GM-CSF, Steel factor and erythropoietin individually to the cultures, W1 cells did not constitutively express mRNA for any of these cytokines. W1 colony growth was markedly suppressed by exogenous TNF-alpha which contrasts sharply with the autocrine growth promoting effect of TNF-alpha on myelomonocytic elements of JCML in 'chronic' phase. The inhibitory effect of TNF-alpha on W1 cells was not due to downregulation of IL-1 production. The IL-1-dependent growth of W1 cells appeared to be unique because none of five other pre-B lineage ALL cell lines established as controls showed an autocrine growth loop via IL-1. W1 cells provide a valuable opportunity to examine the relationship of monosomy 7, B-lineage acute lymphoblastic leukemia, aberrant genetic expression of cytokines and their receptors, and IL-1 mediated autocrine cell growth in cancer.
Leukemia 1995 May
PMID:B-lineage lymphoid blast crisis in juvenile chronic myelogenous leukemia: II. Interleukin-1-mediated autocrine growth regulation of the lymphoblasts. 776 52

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.
Leukemia 1994 May
PMID:Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes. 818 40


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