Results of the Japanese Childhood Acute Myeloid Leukemia 99 Protocol for Down Syndrome and Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 276-276 ◽  
Author(s):  
Kazuko Kudo ◽  
Seiji Kojima ◽  
Ken Tabuchi ◽  
Eisaburo Ishii ◽  
Hiromasa Yabe ◽  
...  

Abstract Purpose: Recent multi-institutional studies have reported that children with Down syndrome (DS) and acute myeloid leukemia (AML) have a favorable outcome with less intensive chemotherapy. Based on our previous trial (Kojima, et al: Leukemia; 14:786,2000), the Japanese Childhood AML Cooperative Study Group conducted the AML-Down protocol study designed for children with DS and AML. Patients and Method: Between February 2000 and June 2004, 72 children (44 boys, 28 girls; median age, 1 year; range, 7 months to 7 years) were enrolled in this study. The median white blood cell count was 5,800/10−9 L. The median follow-up period was 3 years (range, 9 months to 5 years). Acute megakaryocytic leukemia (M7) was diagnosed most often (90%). The treatment regimen consisted of 5 cycles of Ara C 100mg/m2 (1-hour infusion) x 7 days, THP-ADR 25mg/m2 x 2 days, and etoposide 150mg/m2 x 3days. No prophylaxis against CNS leukemia was included. Results: Among the 72 children, 69 achieved complete remission (CR) after 1 to 2 cycles of induction therapy, with no deaths occurring during the induction period. One of 3 patients with induction failure achieved CR after another intensified chemotherapy. Eight patients relapsed during chemotherapy. One relapsed while off therapy and successfully entered a second remission after an intensified chemotherapy, followed by an allogeneic bone marrow transplant. There was no CNS relapse alone, although 1 patient relapsed in the bone marrow and CNS simultaneously. Eight relapsed patients and 2 refractory patients died without achieving a remission. The cause of death was pneumonia in 4 patients and disease progression in 7 patients. One patient died from pneumonia during the first CR. The CR rate, 3-year survival rate, and event-free survival (EFS) rate were 97.2%, 84.4%, and 83.0%, respectively. In a univariate analysis of factors that predict EFS, we found that the presence of monosomy 7 cytogenetic abnormality at diagnosis, and response to induction therapy were predictive factors for EFS. Neither age older than 2 years nor higher white blood cell count at diagnosis were statistically significant risk factors. Children with monosomy 7 had more adverse outcomes than those without monosomy 7 (41.7% vs 86.4%, p=0.02). Discussion: Our AML protocol specified for children with DS and AML does not include high-dose Arac and is much less intensive than other protocols used for treatment of these children. However, this less intensive regimen leads to an excellent outcome. In contrast to a previous study reported from CCG (Children’s Cancer Group) in the United States, age was not a significant risk factor. However, monosomy 7 is a poor prognostic factor in children with AML, whether or not they have DS. Our study strongly suggests that children with DS and AML can be treated successfully with a less intensive chemotherapy regimen that does not include high-dose Arac.

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-39
Author(s):  
Thanawat Rattanathammethee ◽  
Pokpong Piriyakhuntorn ◽  
Sasinee Hantrakool ◽  
Chatree Chai-Adisaksopha ◽  
Ekarat Rattarittamrong ◽  
...  

Background : The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse and may play a role in clinical decisions regarding antimicrobial de-escalation with predictive complications. However, there are few reports of microbiota alteration of adult acute myeloid leukemia (AML) patients. Methods : Stool samples of each treatment-naïve AML patient were collected the day before the initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. Results : Ten AML patients (4 men and 6 women) were included with a median age of 39 years (range: 19-49). Twenty-four stool samples were collected and assigned into three groups: (1) pretreatment (n = 10); (2) first date of febrile neutropenia (n=9); and (3) first date of bone marrow recovery (n=5). All of patients developed febrile neutropenia; three patients had detectable infectious organisms and all of these cases had invasive pulmonary aspergillosis with two being co-infected with Pseudomonas pneumonia and Escherichia coli septicemia. Median absolute neutrophil count was 2.85 x 109/L (range: 1.42-7.67 x 109/L), 0.04 x 109/L (range: 0.01-0.43 x 109/L) and 3.65 x 109/L (range: 2.09-5.78 x 109/L) at pretreatment, first date of febrile neutropenia and first date of bone marrow recovery, respectively. At the phylum level, Firmicutes dominated over the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. At the genus level, Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference of 20.2, [95%CI (5.9, 34.6)]; P <0.01) whileBacteroides and Escherichia notably declined during the same period (mean difference of -11.7, [95%CI (-21.9, -1.4)]; P= 0.027 and -11.6, [95%CI (-22.7, -0.4)]; P = 0.034, respectively). At the operational taxonomic units (OTUs) level, there was a significantly higher level of overall richness in the pretreatment period than in the febrile neutropenic episode (mean OTUs of 203.1 vs. 131.7; P = 0.012). Both of the diversity indexes of Shannon and Simpson showed a significant decrease in the febrile neutropenic period. Conclusions : Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow. Figure Disclosures No relevant conflicts of interest to declare.


Blood ◽  
1990 ◽  
Vol 76 (3) ◽  
pp. 480-488 ◽  
Author(s):  
AK McMillan ◽  
AH Goldstone ◽  
DC Linch ◽  
JG Gribben ◽  
KG Patterson ◽  
...  

Abstract For younger patients with acute myeloid leukemia (AML), an allogeneic transplant from a matched sibling may afford the best chance of cure. In patients who are older or without a matched sibling donor, dose intensification can be achieved with an autologous bone marrow transplant (ABMT). We report here the results of a high-dose chemotherapy regime with nonpurged ABMT in 82 adult patients in first remission of AML with a median follow-up of 31 months. The median age was 40 years (range 16 to 57 years). The median interval between remission and ABMT was 5 months (range 1 to 12 months). Twenty-eight of these patients received a second course of the same high-dose chemotherapy and ABMT. The procedure related mortality rate was 6%. The projected leukemia-free survival (LFS) at 5 years is 48% for all 82 patients and 50% for the 76 patients with no known preceding myelodysplastic syndrome. For those patients with primary AML who received a double ABMT the projected LFS is 67%. The interval between remission and ABMT did not predict for either relapse or LFS. ABMT using a multidrug chemotherapy protocol is less toxic than allogeneic BMT yet results in a similar LFS.


Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1391-1395 ◽  
Author(s):  
RA Brown ◽  
SN Wolff ◽  
JW Fay ◽  
L Pineiro ◽  
RH Jr Collins ◽  
...  

Relapse is a major cause of treatment failure following allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). To reduce the risk of relapse following BMT for patients with hematologic malignancy, our group developed a novel preparative regimen which combines high-dose etoposide with cyclophosphamide and total body irradiation (VPCyTBI). We now report the outcome of therapy with VPCyTBI followed by allogeneic BMT for 40 patients with AML in untreated first relapse. With the exception of increased stomatitis, the toxicity of this regimen was similar to that reported by others for CyTBI. Forty-four months after transplant the actuarial probabilities of disease-free survival (DFS), persistent or recurrent leukemia, and transplant related mortality were .29, .44, and .47 respectively. DFS was improved (P < .01) and risk of persistent or recurrent leukemia reduced (P = .005) among patients with significant (grade > or = 2) acute GVHD. Patients with 30% or more blasts on pre-BMT bone marrow examination were not at increased risk for persistent or recurrent leukemia. We conclude that VPCyTBI with allogeneic BMT is effective therapy for AML in untreated first relapse and that a randomized trial comparing this regimen with CyTBI is warranted.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 916-916 ◽  
Author(s):  
Todd A. Fehniger ◽  
Alissa Nelson ◽  
Kathryn Trinkaus ◽  
Camille N. Abboud ◽  
Amanda F. Cashen ◽  
...  

Abstract AML patients over the age of 60 years have a poor prognosis, share disease characteristics with myelodysplastic syndrome (MDS) patients, and warrant novel therapeutic approaches. Lenalidomide has immunomodulatory and anti-neoplastic properties which can induce morphologic and cytogenetic responses in MDS patients, including those with excess blasts. We hypothesized that lenalidomide may be active against AML, and have employed a high dose strategy without dose reductions for hematologic toxicities. Here, we report preliminary results from a phase II study of high dose lenalidomide for front-line treatment of AML ≥ 60 without chromosome 5q deletion or favorable cytogenetics. Treatment included 2 cycles of high dose lenalidomide (50mg/day x 14 days, 30 days of rest, 50mg/day x 21 days), followed by maintenance therapy (10 mg/day) in non-progressing patients. Fifteen patients were enrolled in the first stage between 2/27/07 and 8/3/07. Median age was 71 years (range 60–86 years); ECOG performance status was 0 (4/15, 27%), 1 (10/15, 67%), or 2 (1/15, 7%); 11/15 (73%) patients were male; and 5/15 (33%) patients had prior MDS. Cytogenetics were normal (n=9), loss of chromosome 7 (n=2), loss of chromosome 20 (n=1), trisomy 13 (n=1), or complex (n=2). Overall, the treatment regimen was well tolerated. In the first stage of the study, 12/15 patients are evaluable for day 15 bone marrow and peripheral blood blast changes following the initial high dose lenalidomide cycle (50 mg/day x 14 days). Pre-therapy WBC counts (mean ± SEM) were 13,825 ± 4,447/uL (range 1,100–45,300/uL) and day 15 WBC counts were 4,742 ± 2,136/uL (range 300–24,400/uL). Day 15 bone marrow myeloblast percentages were significantly reduced in 9/12 patients (mean ± SEM decrease of 53 ± 10%, P=0.01, range 18–100%). In addition, the bone marrow blast index (% cellularity x fraction of blasts) decreased significantly after 14 days of high dose lenalidomide (mean ± SEM reduction of 66 ± 11%, P=0.02). Moreover, 5/8 patients with circulating blasts at diagnosis showed clearance of their peripheral blasts at day 15. These findings suggest that lenalidomide is an active agent against acute myeloid leukemia. Results on AML blast changes, response by international working group criteria, and toxicities in this patient cohort with ≥4 months of follow-up will be updated and presented.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4476-4476
Author(s):  
Jingyan Xu ◽  
Jian Ouyang ◽  
Rong-Fu Zhou

Abstract Abstract 4476 Hematopoietic Stem Cell Transplantation (HSCT) from partially HLA-matched (haploidentical) family donors represents a promising therapy for high-risk acute myeloid leukemia (AML). However, for patients with AML relapsed after HSCT from an HLA-mismatched familial donor, there is no standard therapy. They may receive conventional chemotherapy, cyclosporine withdrawal, second HSCT, and donor leukocyte infusion (DLI) with or without prior mobilization. Recently, combination chemotherapy and DLI showed achieving hematologic remission. We report a case of successful combination chemotherapy and donor leukocyte infusions from original donor in a patient with AML relapsing 6 years after HSCT from an HLA-Mismatched Familial Donor. A 37-year-old male presented with fever in June 2003.Bone marrow aspirate confirmed the diagnosis of AML(M5 subtype according to FAB classification). The patient initially received intensive chemotherapy. However, the patient with AML that was refractory to conventional therapy. He received HSCT in first CR from his mother 1-loci HLA-mismatched (HLA-A) using BuCY- Conditioning regimen on June 11, 2004. He showed a medullary relapse 6 years after HSCT. His bone marrow blast counts exceeded 80% with 8.25% of donor karyotypes (46 XX FISH). We decided to try to use his mother as the donor for DLI. Cytoreductive chemotherapy was commenced prior to DLI. He was treated twice with DLI on August 02, 2010 and September 23, 2011. He was treated chemotherapy before in first DLI, chemotherapy regimens; FLAG-ida [fludarabine 30 mg/m2/d from day-6 to-2 of cell infusion, cytosine arabinoside 2 g/m2/d from day-6 to-2 of cell infusion, idarubicine 20 mg/d day-1 and G-CSF 300μ g/day from day-7 to +30]. The donors received G-CSF 10μ g/kg subcutaneously daily starting day-3 of cell infusion for 5 days. Donor peripheral blood mononuclear cells were collected by CS-3000 Plus cell separator (Baxter Corp.) on the fifth days of G-CSF administration and infused through a central venous catheter into the patients on the same day. 8.33×107/kg mononuclear cells, 6×107/kg CD3+ cells were reinfused without manipulation. Cyclosporine at the dose of 3 mg/kg were administered for the prevention of GVHD. On days 36 Bone marrow blast counts exceeded 45% with 44% of donor karyotypes (46 XX FISH) after first Chemo-DLI. He received cyclosporine withdrawal. He was treated chemotherapy by low-dose Ara-C and aclarubicin with concomitant use of G-CSF before in second DLI.,chemotherapy regimens;CAG[ Low-dose Ara-C was given subcutaneously at a dosage of 10 mg/m2 every 12 hours on days-14 to-1. Aclarubicin was administered intravenously at a dosage of 7 mg/m2 on days-14 to-7. Recombinant G-CSF was given subcutaneously at a dosage of 200μ g/m2 per day on days-14 to-1]. On day 0,1.4×108/kg mononuclear cells,1×108/kg CD3+ cells were reinfused. On days 25 bone marrow examination showed CR with 89% of donor karyotypes (46 XX FISH). He was treated consolidation chemotherapy by regimens; CAG.On days 62 bone marrow examination showed CR with 100% of donor karyotypes (46 XX FISH). He developed chronic GVHD with limited disease at day 123 of DLI. In the patient whose cGVHD resolved with the use of steroid, cyclosporine plus methotrexate. The patient died from pneumonia without evidence of recurrent leukemia on day +230. From the cases reported, combination chemotherapy and subsequent mobilized DLI produced a CR with AML in relapse six years after HLA-Mismatched transplantation. We demonstrate that of the patient who relapsed after 6 years, treatment with chemotherapy followed by intensive chemotherapy followed by DLI, can effectively salvage a patient with attainment of durable remissions. Although limited by the small number of one patient, AML in relapse six years after HLA-Mismatched transplantation requires particular attention in future studies, as well as in designing future treatment programs. Clearly a large number of patients is required to confirm the real efficacy of this treatment. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5204-5204
Author(s):  
Rosa Greco ◽  
Annamaria Petrungaro ◽  
Anna Grazia Recchia ◽  
Laura De Stefano ◽  
Sabrina Bossio ◽  
...  

Abstract Background: Older patients (pts) with acute myeloid leukemia (AML) have a particularly dismal outcome, because of adverse features of AML in the elderly and frailty. The median duration of complete remission (CR) last less than 1 year. The optimal management of older AML pts in daily clinical practice has not been determined. Regular treatment options include best support care, low dose cytarabine (Ara-c) and intensive chemotherapy (anthracycline combined with ara-c). Recently, the DNA methyltransferase inhibitor Azacitidine (AZA) has demonstrated significant activity and favorable tolerability in AML pts also showing a survival advantage. Materials and Methods: Between May 2013 and July 2016, at our institution, 19 pts with a diagnosis of AML (13 males and 7 females) were judged to be ineligible for intensive chemotherapy due to age or comorbidities. They received a 5-day regimen of cytoreductive chemotherapy with ara-c at a dosage of 100 mg\mq\day i.v. continuous infusion. On the sixth day, on termination of Ara-c infusion, all pts had ≤30% bone marrow blasts. Therefore, AZA was administered at a dosage of 75 mg\mq\day subcutaneously for 7 days, continuing the therapy every 28 days. The median age of pts was 75 years (range, 49 to 79 years), with 17 pts (89%) aged over 65 years. Six pts (32%) had poor molecular and cytogenetic risks markers, and six other pts (32%) had either antecedent myelodisplastic/myeloproliferative diseases or therapy related AML. The response to therapy according to the AML IWG criteria was assessed by bone marrow aspiration immediately after Ara-c infusion, after one AZA cycle and every 6 months thereafter. Baseline pts characteristics are summarized in Table 1. Results: The median number of administered AZA cycles was 6 (range, 1-25 cycles). Fifty eight percent (11/19) of pts received ≥6 AZA clycles. The median overall survival was 6 months (range, 1-26 months). According to AML IWG criteria, 8 pts (42%) achieved CR after Ara-c and a single AZA cycle. Of these, 5 pts (62%) are currently alive in CR, with median duration of response of 7 months (range: 5-12 months), while 3 pts (38%) died after 4, 12, and 22 months after diagnosis. One pt (5%) achieved a partial response (PR) after one AZA cycle, maintaining at present the same response after 3 months of therapy. Other 8 pts (42%) obtained stable disease (SD). Of these, 3 pts (37%) are currently in SD after 2, 8 and 10 months of therapy, while 5 pts (64%) died within a median of 5 months (range: 2 - 18 months) after AML diagnosis. Finally 1 pt (5%) was refractory dying after 2 months of diagnosis, and another pt (5%) died after first AZA cycle for sepsis. Fever and infections were the most common non-hematologic toxic events after Ara-c chemotherapy and first AZA cycle (17/19 pts, 90%). While subsequent AZA cycles were well tolerated. Conclusion: We suggest that the use of Ara-c-AZA combination is feasible in elderly AML pts. However, the relatively small number of pts studied and short follow up preclude definitive conclusion. The study is still accruing patients. Disclosures No relevant conflicts of interest to declare.


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yasuhiro Tanaka ◽  
Atsushi Tanaka ◽  
Akiko Hashimoto ◽  
Kumiko Hayashi ◽  
Isaku Shinzato

Myelodysplastic syndrome (MDS) terminally transforms to acute myeloid leukemia (AML) or bone marrow failure syndrome, but acute myeloid leukemia with basophilic differentiation has been rarely reported. An 81-year-old man was referred to our department for further examination of intermittent fever and normocytic anemia during immunosuppressive treatment. Chromosomal analysis showed additional abnormalities involving chromosome 7. He was diagnosed as having MDS. At the time of diagnosis, basophils had not proliferated in the bone marrow. However, his anemia and thrombocytopenia rapidly worsened with the appearance of peripheral basophilia three months later. He was diagnosed as having AML with basophilic differentiation transformed from MDS. At that time, monosomy 7 was detected by chromosomal analysis. We found that basophils can be confirmed on the basis of the positivity for CD203c and CD294 by flow cytometric analysis. We also found by cytogenetic analysis that basophils were derived from myeloblasts. He refused any chemotherapy and became transfusion-dependent. He died nine months after the transformation. We should keep in mind that MDS could transform to AML with basophilic differentiation when peripheral basophilia in addition to myeloblasts develops in patients with MDS.


2020 ◽  
Author(s):  
Thanawat Rattanathammethee ◽  
Pimchanok Tuitemwong ◽  
Parameth Thiennimitr ◽  
Phinitphong Sarichai ◽  
Sarisa Na Pombejra ◽  
...  

AbstractIntestinal bacterial flora of febrile neutropenic patients had significantly diverse. However, there were scanty reports of microbiota alteration of adult patients with acute myeloid leukemia (AML). Stool samples of each treatment-naïve AML patient were collected at the day before induction chemotherapy initiation (pretreatment), first day of neutropenic fever and first day of bone marrow recovery. Bacterial DNA was extracted from stool and sequenced bacterial 16s ribosomal RNA genes by next-generation sequencing. Relative abundance, overall richness, Shannon’s diversity index and Simpson’s diversity index were calculated. Ten cases of AML patients (4 men and 6 women) were included with median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes were dominated over the period of neutropenic fever and subsequent declined after bone marrow recovery contrast to Bacteroidetes and Proteobacteria. Enterococcus was more abundant at febrile neutropenia period compared to pretreatment while Bacteroides and Escherichia was notably declined during the febrile neutropenia. At the operational taxonomic units (OTUs) level, there was significant higher level of overall richness of pretreatment period than febrile neutropenic episode. Both of the diversity indexes of Shannon and Simpson were considerably decreased at febrile neutropenic period. Adult AML patients with first episode of febrile neutropenia after initial intensive chemotherapy demonstrated the significant decrease of gut microbiota diversity and the level of diversity consistently remained constant despite of bone marrow recovery.


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