Prospective Study of 90 Children Requiring Treatment for Juvenile Myelomonocytic Leukemia or Myelodysplastic Syndrome: A Report From the Children’s Cancer Group

2002 ◽  
Vol 20 (2) ◽  
pp. 434-440 ◽  
Author(s):  
William G. Woods ◽  
Dorothy R. Barnard ◽  
Todd A. Alonzo ◽  
Jonathan D. Buckley ◽  
Nathan Kobrinsky ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Prospective Study ◽  
De Novo ◽  
Refractory Anemia ◽  
Juvenile Myelomonocytic Leukemia ◽  
Allogeneic Bone ◽  
Monosomy 7 ◽  
Cancer Group ◽  
De Novo Aml ◽  
Myelomonocytic Leukemia

PURPOSE: We report the first large prospective study of children with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) treated in a uniform fashion on Children’s Cancer Group protocol 2891. PATIENTS AND METHODS: Ninety children with JMML, various forms of MDS, or acute myeloid leukemia (AML) with antecedent MDS were treated with a five-drug induction regimen (standard or intensive timing). Patients achieving remission were allocated to allogeneic bone marrow transplantation (BMT) if a matched family donor was available. All other patients were randomized between autologous BMT and aggressive nonmyeloablative chemotherapy. Results were compared with patients with de novo AML. RESULTS: Patients with JMML and refractory anemia (RA) or RA-excess blasts (RAEB) exhibited high induction failure rates and overall remission of 58% and 48%, respectively. Remission rates for patients with RAEB in transformation (RAEB-T) (69%) or antecedent MDS (81%) were similar to de novo AML (77%). Actuarial survival rates at 6 years were as follows: JMML, 31% ± 26%; RA and RAEB, 29% ± 16%; RAEB-T, 30% ± 18%; antecedent MDS, 50% ± 25%; and de novo AML, 45% ± 3%. For patients achieving remission, long-term survivors were found in those receiving either allogeneic BMT or chemotherapy. The presence of monosomy 7 had no additional adverse effect on MDS and JMML. CONCLUSION: Childhood subtypes of MDS and JMML represent distinct entities with distinct clinical outcomes. Children with a history of MDS who present with AML do well with AML-type therapy. Patients with RA or RAEB respond poorly to AML induction therapy. The optimum treatment for JMML remains unknown.

Chronic Myelomonocytic Leukemia With Preexisting Myelodysplastic Syndrome Or Myeloproliferative Neoplasm: Two Stages Of One Disease With Poor Prognosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1342-1342 ◽  
Author(s):  
Yin Xu ◽  
Aine Yung ◽  
Brian Kwok ◽  
Karen Macdonell ◽  
Bashar Dabbas ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
De Novo ◽  
Myeloproliferative Neoplasm ◽  
Chronic Myelomonocytic Leukemia ◽  
Chromosome Abnormalities ◽  
Refractory Anemia ◽  
Jak2 Mutation ◽  
Cytogenetic Abnormalities ◽  
Two Stages ◽  
Myelomonocytic Leukemia

Abstract Introduction Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy characterized by persistent monocytosis with features of a myelodysplastic syndrome (MDS) and/or myeloproliferative neoplasm (MPN). While most cases present as de novo disease, a subset of CMML has been described in the literature to evolve from a preexisting MDS (MDS-CMML). CMML with preexisting MPN (MPN-CMML) has not been characterized to our knowledge. It is uncertain whether CMML patients with preexisting MDS or MPN have one or more disease processes and if such patients behave differently from patients who present with de novo CMML. In an attempt to address these questions, we compared the clinicopathologic features between groups of MDS-CMML, MPN-CMML, and de novo CMML in the present study. Methods 126 cases with newly diagnosed CMML were retrieved from our database over a 3-year period. 22 cases had preexisting MDS (n=15) or MPN (n=7). Prior diagnoses of MDS included refractory anemia (n=5), refractory anemia with ring sideroblasts (n=2), MDS with isolated 5q deletion (n=1), refractory cytopenia with multilineage dysplasia (n=6), and refractory anemia with excess blasts-1 (n=1). Prior diagnoses of MPN included essential thrombocythemia (n=1), primary myelofibrosis (n=3), and MPN NOS (n=3). Cytogenetic studies were performed in all cases. Other parameters obtained included age, gender, hemoglobin, white blood cell count, monocytes, platelets, bone marrow blasts and histology, and JAK2/MPL mutations. 22 consecutive cases of de novo CMML were included for comparative analysis. Results CMML with preexisting MDS or MPN comprised 17% of CMML (22/126 patients). Among these 22 patients, 15 were male and 7 female with a median age of 79 (range 61-86) years. Median age of the patients at CMML stage was similar to that of patients with de novo CMML (77 years; range 65-89). The median time between disease presentation as MDS or MPN and CMML was 22 months. Patients presented with marked monocytosis at the CMML stage (mean: 23% and 4564/uL) as compared to the stage of MDS (mean: 13% and 794/uL; p<0.001) or MPN (mean: 6.4% and 1216/uL; p<0.001); and the monocyte count was similar to that present in de novo CMML (mean: 24% and 4313/uL). Marrow blasts were significantly increased at the CMML stage as compared to the stage of MDS (mean: 5.3 vs. 1.6; p=0.017), MPN (mean: 5.1 vs. 1.9; p=0.048), or de novo CMML (5.2 vs. 1.9; p=0.009). There was no significant difference in average hemoglobin, platelet count or marrow cellularity between cases at the two disease stages or among the MDS-CMML and MPN-CMML subgroups. However, the marrows of MPN-CMML showed significantly increased diffuse reticulin fibrosis (p=0.002) and marked megakaryocytic hyperplasia (p=0.002) as compared to MDS-CMML. CMML with preexisting MDS or MPN is more frequently associated with cytogenetic abnormalities than de novo CMML (50% vs. 23%), although this difference did not reach statistical significance (p=0.116). 8 (36%) cases had chromosome abnormalities at the MDS or MPN stages; 7 (87%) of the 8 cases demonstrated persistent chromosome abnormalities at the CMML stage. In addition, 4 (18%) patients acquired chromosome abnormalities at the CMML stage. JAK2 mutation was seen in 1 (7%) of 15 cases of MDS-CMML and 4 (57%) of 7 cases of MPN-CMML. Notably, 2 cases of JAK2 positive MPN became JAK2 negative at the CMML stage; one of the patients had been previously treated with a JAK2 inhibitor. No MPL mutation was found in any case. Conclusions CMML with preexisting MDS or MPN is not uncommon. The majority of cases exhibit persistent chromosomal abnormalities from the preexisting MDS or MPN, supporting the notion of one disease with two stages of presentation. The findings of a higher frequency of cytogenetic abnormalities and occasional cytogenetic evolution may suggest that chromosome alteration is one of the mechanisms involved in triggering disease progression to CMML. JAK2 V617F was more frequent in MPN-CMML, which correlated with myelofibrosis and megakaryocytic hyperplasia. However, loss of JAK2 mutation can occur at CMML stage. Loss/inhibition of JAK2 activity may contribute to a change in disease course. Our study revealed that CMML with preexisting MDS or MPN is characterized by more advanced disease with increased marrow blasts and therefore may be associated with a poorer prognosis. Disclosures: No relevant conflicts of interest to declare.

Acute Myeloid Leukemia (AML) - Type Chemotherapy for Newly Diagnosed Children with Myelodysplastic Syndrome (MDS): A Japanese Childhood MDS Study Group Trial MDS99.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4726-4726
Author(s):  
Yoshitoshi Ohtsuka ◽  
Atsushi Manabe ◽  
Jun Okamura ◽  
Seiji Kojima ◽  
Akira Ohara ◽  
...  
Keyword(s):  
Induction Therapy ◽  
De Novo ◽  
Prospective Trial ◽  
Refractory Anemia ◽  
Remission Induction ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Significant Difference ◽  
De Novo Aml

Abstract Background The role of intensive chemotherapy in treatment of childhood MDS has not been clarified yet. We conducted a prospective trial which employed intensive AML-type chemotherapy for children with de novo MDS. Methods Fifteen children aged 1 to 15 years who met diagnostic criteria of the FAB refractory anemia with excess of blasts (RAEB) with more than 10% of blasts in the bone marrow (BM) (RAEB-II) and RAEB in transformation (RAEBT) were prospectively enrolled in the study. Abnormal karyotype was documented in 11 patients including 3 with monosomy 7, 2 with complex karyotype, 1 with trisomy 8. Induction therapy consisted of etoposide (150mg/m2, on days 1–5), cytarabine (200mg/m2/12hr, on days 6–12), and mitoxantrone (5mg/m2, on days 6–10) in all but 1 patient, who received another regimen of AML induction therapy. The use of granulocyte-colony stimulating factor was allowed. Allogeneic stem cell transplantation (SCT) was scheduled after remission induction therapy. The median follow-up for 13 surviving patients was 685 days (58 to 1,476 days). Findings Eleven patients (73%) including 3 with monosomy 7 achieved a complete remission after induction therapy at a median of 40 days (31 to 61 days). Remission was not obtained in the other 4 patients. There was no significant difference in the frequency and severity of toxicity between in patients with RAEB-II/RAEBT and in those with de novo AML. Allogeneic SCT was performed in 13 patients including 9 in the remission at a median of 4 months (2 to 6 months) after the beginning of the therapy. None of nine patients who underwent SCT in the remission relapsed. Although two patients died of the complications of SCT. Overall survival for all the 15 patients at 2 years was 66.8 ± 14.1% (s.e.). Interpretation AML-type induction therapy appears to be safe and effective for children with RAEB with more than 10% of blasts in the BM and RAEBT. Figure Figure

Pediatric Myelodysplastic Syndrome and Juvenile Myelomonocytic Leukemia in Korea: A Nation-Wide, Multicenter, Retrospective Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4630-4630
Author(s):  
Hoon Kook ◽  
Dong Kyun Han ◽  
Hyeong Jin Kang ◽  
Bin Cho ◽  
Nak Gyun Chung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Myelodysplastic Syndrome ◽  
Chronic Gvhd ◽  
Classification Systems ◽  
Juvenile Myelomonocytic Leukemia ◽  
Overall Survival Rate ◽  
Monosomy 7 ◽  
Kaplan Meier ◽  
Myelomonocytic Leukemia

Abstract Recent advances in the diagnosis, molecular pathogenesis, classification and therapy have been made in the field of myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) in childhood. We report a retrospective analysis of children with MDS and JMML diagnosed between 2001 and 2006 in Korea. In total, 135 patients were enrolled from 19 major hospitals with pediatric hematology oncology clinics: MDS, 96 (primary MDS, 77; constitutional anomalies with MDS, 13; treatment-related MDS, 6) and JMML, 39. The incidence of MDS/JMML was around 22.5/year, which is about 6% of childhood leukemia. Various classification systems including FAB, WHO, IPSS, CCC system, and pediatric adjustment of the WHO classification were applied. The median ages at diagnosis were 68 and 10 months in MDS, and JMML, respectively. Males dominated in JMML. Cytogenetic abnormalities were observed in 43% of MDS (monosomy 7, 5; trisomy 8, 3) and in 10% of JMML. Treatment was chosen by each institute’s preference: 34 patients with MDS received AML-type intensive chemotherapy, with complete remission rate of 82.0%. The 5-year Kaplan-Meier overall survival rate was 54% each for MDS and JMML. Survival of MDS patients was influenced by the marrow blast % (P = 0.007) and disease category (P= 0.006). Stem cell transplantations (SCT) were undertaken in 56 patients (MDS, 29; JMML, 27). The sources of stem cells were: bone marrow, 36; umbilical cord, 18; peripheral blood, 2). Matched related transplants were 9 cases. Conditioning was various, but BuCy based regimen was used in 68.4%. Acute GvHD ≥ Grade II was found in 43.8% and chronic GvHD in 35.1%. The 5-year Kaplan-Meier overall survival rate was 55% for MDS, and 57% for JMML. Survival after unrelated transplant was comparable with that of matched related transplants. This analysis inspired the necessity of nation-wide prospective studies in Korea, including morphologic study by a central pathology review board, epidemiologic study, molecular pathophysiologic study, and therapeutic trials incorporating SCTs, or new drugs.

Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.

1997 ◽  
Vol 15 (2) ◽  
pp. 566-573 ◽  
Author(s):  
F Locatelli ◽  
C Niemeyer ◽  
E Angelucci ◽  
C Bender-Götze ◽  
S Burdach ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Myelodysplastic Syndrome ◽  
Marrow Transplantation ◽  
Working Group ◽  
Allogeneic Bone Marrow Transplantation ◽  
Chronic Myelomonocytic Leukemia ◽  
Allogeneic Bone ◽  
European Working ◽  
Myelomonocytic Leukemia

PURPOSE To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.

scholarly journals Korszakváltás a gyermekkori szerzett csontvelő-elégtelenséggel járó kórképek kezelésében Magyarországon

2018 ◽  
Vol 159 (42) ◽  
pp. 1710-1719
Author(s):  
Krisztián Kállay ◽  
Judit Csomor ◽  
Emma Ádám ◽  
Csaba Bödör ◽  
Csaba Kassa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Survival Rate ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Severe Aplastic Anemia ◽  
Juvenile Myelomonocytic Leukemia ◽  
Reduced Intensity Conditioning ◽  
Myelomonocytic Leukemia ◽  
Reduced Intensity

Abstract: Introduction: Acquired bone marrow failures are rare but fatal diseases in childhood. Since 2013, Hungary has been participating as a full member in the work of the European Working Group on uniform diagnostics and therapy in patients with acquired bone marrow failure syndromes. Hypocellular refractory cytopenia of childhood has been emphasized as a frequent entity, transplanted by reduced intensity conditioning with excellent outcomes. Aim: To analyse and compare the results of treatment before and after our joining. Method: A total of 55 patients have been treated in the 8 centres of the Hungarian Pediatric Oncology Network during 5 years between 2013 and 2017 (severe aplastic anemia: 9, myelodysplastic syndrome: 41, juvenile myelomonocytic leukemia: 5 patients). Allogeneic hematopoietic stem cell transplantation was performed in severe aplastic anemia in 7 cases, while antithymocyte globulin was administered in one case and one patient died before diagnosis. In patients with myelodysplastic syndromes, watch and wait strategy was applied in 4, while transplantation in 37 cases. Reduced intensity conditioning was used in 54 percent of these cases. Transplantation was the treatment of choice in all 5 patients with juvenile myelomonocytic leukemia. Results: In the whole patient cohort, the time from diagnosis to treatment was median 92 (3–393) days, while in severe aplastic anemia median 28 (3–327) days only. Grade II–IV acute graft versus host disease occurred in 22.6%, grade III–IV in 6.8% and chronic in 11.2%. All the patients treated with severe aplastic anemia are alive and in complete remission (100%). The overall estimated survival rate is 85.1% in myelodysplastic syndrome, while 75% in juvenile myelomonocytic leukemia. The median follow-up was 30.4 (1.1–62.5) months. There was a remarkable increase in overall survival comparing the data before (1992–2012) and after (2013) joining the international group, 70% vs. 100% (p = 0.133) in severe aplastic anemia and 31.3% vs. 85.1% (p = 0.000026) in myelodysplastic syndrome. Conclusion: Due to a change in the paradigm of the conditioning regimen in hypocellular refractory cytopenia of childhood, the overall survival rate has significantly increased. Orv Hetil. 2018; 159(42): 1710–1719.

Myelodysplastic/Myeloproliferative Neoplasms

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 264-272 ◽  
Author(s):  
Mario Cazzola ◽  
Luca Malcovati ◽  
Rosangela Invernizzi
Keyword(s):  
Clinical Laboratory ◽  
Myeloproliferative Neoplasms ◽  
Chronic Myelomonocytic Leukemia ◽  
World Health ◽  
Refractory Anemia ◽  
Molecular Diagnostic ◽  
Juvenile Myelomonocytic Leukemia ◽  
Lymphoid Tissues ◽  
Ring Sideroblasts ◽  
Myelomonocytic Leukemia

Abstract According to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, myelodysplastic/myeloproliferative neoplasms are clonal myeloid neoplasms that have some clinical, laboratory, or morphologic findings that support a diagnosis of myelodysplastic syndrome, and other findings that are more consistent with myeloproliferative neoplasms. These disorders include chronic myelomonocytic leukemia, atypical chronic myeloid leukemia (BCR-ABL1 negative), juvenile myelomonocytic leukemia, and myelodysplastic/myeloproliferative neoplasms, unclassifiable. The best characterized of these latter unclassifiable conditions is the provisional entity defined as refractory anemia with ring sideroblasts associated with marked thrombocytosis. This article focuses on myelodysplastic/myeloproliferative neoplasms of adulthood, with particular emphasis on chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts associated with marked thrombocytosis. Recent studies have partly clarified the molecular basis of these disorders, laying the groundwork for the development of molecular diagnostic and prognostic tools. It is hoped that these advances will soon translate into improved therapeutic approaches.

Sign in / Sign up

Export Citation Format

Share Document