Bone Marrow Transplant (BMT) for Acute Myeloid Leukemia (AML) Patients with Translocation (6; 9).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5051-5051
Author(s):  
Abdo S. Haddad ◽  
April Smith ◽  
Brain Bolwell ◽  
Matt Kalaycio
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Bone Marrow Transplant ◽  
Induction Chemotherapy ◽  
High Risk Patient ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Small Series

Abstract Response and long term outcome to chemotherapy treatment in patient with AML may differ significantly depending on many factors identified at the time of diagnosis. Age, cytogenetics, and history of myelodysplasia are predictors of survival in patients undergoing induction chemotherapy. AML characterized by t (6;9) (p23; q34) - DEK/CAN fusion occurs only in 1–5% of AML cases. This translocation involves recurrent breakpoints in the DEK gene on chromosome 6p23 andin the CAN gene on chromosome 9q34. It predicts a poor outcome with chemotherapy alone and BMT is usually recommended as a result. However, the curative potential of BMT for t(6; 9) AML patients is unknown. We reviewed our experience treating AML with BMT. Five patients with t (6; 9) AML and one with high-risk myelodysplastic syndrome (MDS) underwent BMT following induction chemotherapy. The prep regimen was Busulfan/Cyclophosphamide in all but one patients and standard GVHD prophylaxis was used. No patient received a T-Cell depleted graft. The median follow up of survivors was 24 months (9–38 months). Our small series provides intriguing data suggesting the potential for cure of patients with AML and t (6; 9). While our data requires confirmation in a larger series of patients, our results provide a rationale to recommend BMT to these high risk patient with AML. Table 1: Characteristics Pt. # Dx Date Age BMT Remission tatus GVHD Relapse A/D Months (Pt. #) Patient number, (Dx) Diagnosis, (BMT) bone marrow transplant date, (GVHD) graft versus host disease, (A/D) Alive/Dead from initial diagnosis, (CR) Complete remission, Matched unrelated donor, and (MSD) Matched sibling donor 1 10/04 37 MSD 6/05 CR1 Yes No A +34 2 06/04 36 MUD 10/06 CR2 NO No A +38 3 03/06 50 MUD 7/06 CR1 NO Yes D +13 4 09/05 20 MUD 12/05 CR1 NO No A +24 5 11/06 39 MSD 2/07 CR1 Yes No A +9 6 10/06 41 MSD 2/07 Refractory No No A +10

Refractory Thrombocytopenia Due to Allo-Immune Anti-CD36 Complicating Unrelated Donor Bone Marrow Transplant in a CD36-Negative Recipient.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4951-4951
Author(s):  
William R. Broderick ◽  
Amir A. Toor ◽  
Brian R. Curtis ◽  
Tulio E. Rodriguez ◽  
Scott E. Smith ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Platelet Transfusion ◽  
Family Members ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Severe Thrombocytopenia ◽  
Allogeneic Bone ◽  
Donor Bone Marrow ◽  
Antibody Titers

Abstract Platelet transfusion refractoriness following allogeneic bone marrow transplantation usually stems from HLA alloimmunization. However other platelet antigens may serve as targets of alloimmune reactivity. A 24-year-old Palestinian male with atypical CML in chronic phase underwent matched unrelated donor bone marrow transplant from a 39-year-old female, HLA-A, B, C and DR allele level matched donor. Conditioning was with busulfan 0.8mg/Kg IV q6 hours day -8 through -4, cyclophosphamide 60mg/Kg IV daily day -3 & -2 and rabbit anti-thymocyte globulin 1.5mg/Kg IV daily day -5 & -4. Graft versus host disease prophylaxis was with mini-dose methotrexate and tacrolimus, with filgrastim given for hematopoietic reconstitution. The cell dose was 1.86x106 CD34+ cells/Kg recipient body weight (3.66x108 mononuclear cells/Kg). Neutrophil engraftment occurred on day +14, and was complicated by a diffuse purpuric skin rash, with hypoxia and pulmonary infiltrates which resolved with corticosteroid therapy. His post-transplant course was also complicated by severe, transfusion refractory thrombocytopenia (to random donor pools, apheresis and crossmatched platelet units) starting on day +5 with platelet counts of <5x103/μL. He developed intra-retinal hemorrhage of the right eye, scleral hemorrhage bilaterally, epistaxis and muco-cutaneous bleeding. During the first 30 days following BMT he received 53 doses of platelets in addition to aminocaproic acid. He did not have DIC, splenomegaly or evidence of microangiopathy. HLA alloantibodies were not identified. Antigen Capture ELISA and flow cytometry for platelet specific antibody identification however demonstrated antibodies specific for CD36 in the patient’s serum (Fig). Platelets from the bone marrow donor typed positive for CD36. IVIG 0.5gm/Kg IV on d+13, 14, and 17 and Rituximab 375mg/m2 IV d + 17, 64, 72, and 82 were administered with no therapeutic response. The patient finally responded to transfusions of platelets collected from family members (parents, siblings and cousins) who were CD36negative. Bone marrow biopsies 2 months and 4 months following transplantation showed no evidence of residual disease with trilineage engraftment and adequate megakaryocytes, normal cytogenetics and >98% donor chimerism. As his immunosuppression has been tapered over time, the antibody titer has declined (Fig) as has his platelet transfusion requirement (41 doses transfused between day 31 and 120). However he remains dependent upon directed donor platelet transfusions from his CD36 negative family members at 120 days from transplant. The CD36 negative phenotype is rare in Caucasians, however, platelets from about 5% of individuals of Asian or African descent lack CD36. DNA sequencing to determine CD36 mutations in this patient is underway. We hypothesize that this patient developed a host vs. graft humoral response against donor derived and transfused platelets resulting in sustained severe thrombocytopenia. Patient serum CD36 antibody titers following transplant Patient serum CD36 antibody titers following transplant

Impact of Surgical Treatment on Paranasal Fungal Infections in Bone Marrow Transplant Patients

1997 ◽  
Vol 116 (6) ◽  
pp. 610-616 ◽  
Author(s):  
Cynthia A. Kennedy ◽  
George L. Adams ◽  
Joseph R Neglia ◽  
G. Scott Giebink
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Surgical Intervention ◽  
Fungal Infections ◽  
Systemic Disease ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Fungal Sinusitis ◽  
Cell Counts ◽  
Immunosuppressed Patients

Invasive fungal sinusitis can develop in immunosuppressed patients. A more complex problem is immunosuppressed patients who have undergone bone marrow transplantation. For a prolonged period, they are both neutropenic and thrombocytopenic. Survival in these patients is poor, and the role for extensive surgical intervention for sinus disease has to be weighed against the risk and the potential that this is a systemic disease. Between January 1983 and June 1993, 29 bone marrow transplant recipients with documented invasive fungal infections of the sinuses and paranasal tissues required surgical intervention. This represents 1.7% of the total 1692 bone marrow transplants performed. There were 22 allogeneic, 6 autologous, and 3 unrelated donor transplants, with two patients receiving two separate grafts. Underlying diseases included 24 hematologic malignancies and 5 other disorders, including 1 aplastic anemia and 1 solid tumor. The mortality rate from the initial fungal infection was 62%. Twenty-seven percent resolved the initial infections but subsequently died of other causes. All patients received medical management, such as amphotericin, rifampin, and colony-stimulating factors, in addition to surgical intervention. Surgical management ranged from minimally invasive procedures to extensive resections including medial maxillectomies. Sixty-one percent of the patients who died of the initial infection had undergone extensive surgical procedures versus 55% of those who resolved the infection. Recovery of neutrophil counts was required to clear the infection but did not necessarily predict a good outcome because 50% of those who died of the infection had experienced neutrophil recovery. White blood cell counts at the time of surgery were not significantly different between the two groups. Prognosis was poor when cranial and orbital involvement and/or bony erosion occurred.

Cytogenetic Remission Status after Induction Chemotherapy for AML and High-Risk MDS Predicts Long-Term Outcome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3009-3009
Author(s):  
Sebastian Balleisen ◽  
Hildebrand Barbara ◽  
Royer-Prokora Brigitte ◽  
Kuendgen Andrea ◽  
Gattermann Norbert ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Intermediate Risk ◽  
Abnormal Karyotype ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Remission Status ◽  
Risk Patients ◽  
Cytogenetic Remission

Abstract Cytogenetic findings at diagnosis have an important impact on prognosis in AML and MDS. Therefore, treatment is commonly stratified according to karyotype. Another important prognostic factor is remission status after induction chemotherapy. However, the diagnosis of remission, and the resulting treatment decisions, are usually not based on cytogenetic findings, but rely on peripheral blood counts and bone marrow blast cell counts. We analysed the prognostic impact of cytogenetic remission status in 115 patients with abnormal karyotype who received induction chemotherapy because of AML (n=102) or MDS (n=13). Initial karyotypes were as follows: 14x t(15;17), 9x t(8;21), 5x inv(16), 55 intermediate-risk, and 32 complex karyotypes. The following induction protocols were used: 38x TAD, 4x HAM, 25x Ida-Ara, 36x ICE, and 3x other protocols. Eleven patients received induction chemotherapy plus ATRA. 23 patients underwent allogeneic transplantation after induction therapy, either as late consolidation in cytologic remission (CR), or as standard treatment in high-risk patients. 78 patients achieved CR, 21 achieved partial remission (PR), and 16 patients were non-responders (NR). There were 26 patients who reached cytological CR but still showed an abnormal karyotype after induction. 17 of these 26 patients had been classified as standard-risk and therefore did not receive intensified consolidation. In 59 patients, a normal karyotype was found after induction therapy. 24 of 28 patients belonging to low-risk cytogenetics (t15;17, t8/21, or inv16) achieved cytogenetic complete remission (CCR). The CCR rate was much lower in patients with intermediate-risk cytogenetics (24/55) and patients with complex karyotypes (11/32). Median survival in the group achieving CCR was 40 months, as compared to 11 months in patients with persistence of abnormal karyotype after induction (p<0,00005). The difference remained highly significant when calculated only for patients with complex or intermediate-risk karyotypes (median survival 29 vs 11 months). Conclusions: Cytogenetic analysis after induction chemotherapy is useful to detect residual disease and therefore provides meaningful information in addition to cytology. Achieving cytogenetic remission after induction therapy is strongly correlated with a better long-term outcome. Patients with a persisting abnormal karyotype must be regarded as high-risk patients who should receive intensified treatment.

Outcome of Bone Marrow Transplantation for Myelofibrosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 170-170 ◽  
Author(s):  
Karen Ballen ◽  
Kathleen A. Sobocinski ◽  
Mei-Jie Zhang ◽  
Mukta Arora ◽  
Mary M. Horowitz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Survival Rates ◽  
Allogeneic Transplantation ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Karnofsky Performance Score ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Sibling Donor

Abstract Myelofibrosis is a myeloproliferative disorder characterized by splenomegaly, bone marrow fibrosis and immature white and red blood cells. Allogeneic transplantation is the only curative therapy. In this study, we analyzed the outcomes of 320 patients receiving allogeneic hematopoietic stem cell transplants for myelofibrosis between 1989 and 2002, using the databases of the Center for International Bone Marrow Transplant Research (CIBMTR), a research affiliation of the International Bone Marrow Transplant Registry (IBMTR) and the National Marrow Donor Program (NMDP). This is the largest report of transplantation for myelofibrosis. Patients received a variety of conditioning and graft versus host disease prophylaxis regimens. Most patients received ablative conditioning with either TBI (n=117) or Busulfan (n=150) and cyclophosphamide. Bone marrow was the graft source in 208 patients. 170 transplants were from an HLA-identical sibling donor, 117 from an unrelated donor (MUD), and 33 from an alternative related donor. Median ages at transplant were 45 (&lt;1–73), 47 (1–69) and 40 (&lt;1–65) years, respectively. Median follow up times for survivors were 41 (3–136), 48 (4–124) and 32 (7–118) months, respectively. Both early and long-term survival rates were higher after HLA-identical sibling transplantation. 100-day mortality was 22% after sibling transplants, 42% after MUD transplants, and 27% after alternative family donor transplants. Corresponding 5 year overall survival rates were 39%, 31% and 31%. In multivariate analysis of 215 adult recipients of myeloablative transplants, having an HLA-identical sibling donor, Karnofsky performance score greater than or equal to 90%, younger age, more recent date of transplantation, and absence of blasts in peripheral blood prior to transplantation correlated with better survival. Among 18 patients with all of these favorable factors, the five-year probability of survival was 81%. In conclusion, 1) allogeneic transplantation cures approximately 1/3 of patients with myelofibrosis; 2) young patients with HLA-matched sibling donors have superior survival; 3) results have improved over the last decade. Future research directions will focus on the use of nonmyeloablative conditioning regimens for myelofibrosis.

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