Incidence Of Extramedullary Relapse Research Articles

INCIDENCE, RISKS AND OUTCOME OF EXTRA MEDULLARY RELAPSE IN ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN AND ADULTS: A RETROSPECTIVE COHORT STUDY

Extra medullary relapse (EMR) is the major concern of treatment failure in acute lymphoblastic leukemia (ALL). Hence, their early detection may improve prognosis. Aim of the study is to identify risk factors and outcome of EMR patients with and without concurrent medullary relapse. We retrospectively analyzed 113 patients of ALL who presented with EMR in a tertiary cancer care hospital. Patients were divided into two groups; Group 1, combined EMR (with medullary relapse) and Group 2, isolated EMR (without medullary relapse). Clinical characteristics including total leukocyte count (TLC) & peripheral blood blast percentage during presentation, phenotype, initial central nervous system (CNS) involvement and BCR-ABL translocation were analyzed to identify risk factors for EMR. Incidence of EMR in our study was 15.7% (113/720 patients). Two year incidence of combined EMR and isolated EMR was 10.1% and 5.5% respectively. CNS, followed by testis was common sites of EMR. TLC >50x109/L and peripheral blood blast percentage >50% at presentation was common in Group 1. BCR-ABL translocation was frequent in Group 2 and in adults compared to children (p=0.027). While Group 1 patients presented with leukocytosis (TLC >10X109/L), Group 2 patients presented with leukopenia (TLC <4X109 p=0.001). p=0.001).>50X109/L and BCR-ABL translocation were identified as risk factors for combined EMR (p=0.004) and for in adults with isolated EMR (p=0.001) respectively.

Clinical effects of CD45 on the prognosis of extramedullary myeloma relapse.

The incidence of extramedullary relapse (EMR) arising during the clinical course of multiple myeloma (MM) has increased in recent years. Therefore, we herein investigated the effects of immunophenotyping on the prognosis of MM patients with EMR. We conducted a retrospective review on data collected from MM patients with EMR between January 2007 and December 2018 at the Japanese Red Cross Society Wakayama Medical Center. Patient characteristics at the diagnosis of EMR, the prognostic significance of immunophenotyping and other factors were evaluated. Extramedullary relapse was detected in 55 of 231 patients (23.8%). At the diagnosis of EMR, CD45, the leucocyte common antigen, was detected in 54.5% of cases. CD45 negativity in bone marrow correlated with thrombocytopenia and higher serum LDH levels. Moreover, high-risk cytogenetics was more frequently observed in CD45- than in CD45+patients. A univariate analysis showed that overall survival (OS) was significantly shorter in CD45- than in CD45+patients. Thrombocytopenia, higher serum LDH levels and high-risk cytogenesis were also associated with shorter OS. A multivariate analysis confirmed that CD45 negativity, higher serum LDH levels and high-risk cytogenesis were independent adverse prognostic factors for OS. A Kaplan-Meier analysis revealed the potential of CD45- as a prognostic factor in patients with EMR and that it correlated with shorter survival. The present results showed that the expression of CD45 in the neoplastic plasma cells of MM patients with EMR was associated with patient prognosis independent of other prognostic factors. The establishment of a treatment strategy for EMR patients with CD45- MM cells is needed to improve poor outcomes.

Azacitidine in the treatment of extramedullary relapse of AML after allogeneic hematopoietic cell transplantation

Extramedullary relapse of AML after allogeneic hematopoietic SCT (HSCT) is rare and less well-defined than systemic disease relapse. In a European Group for Blood and Marrow Transplantation (EBMT) study, the incidence of extramedullary relapse after HSCT was as low as 0.65% in AML.1 However, other studies have reported an incidence of up to 20% among long-term survivors.1, 2, 3, 4, 5, 6 There are no established guidelines for clinical decision making pertaining to the treatment of extramedullary relapse after HSCT.7 Common practice entails a combination of localized radiation, systemic chemotherapy, immunotherapy with donor lymphocyte infusions (DLI), and repeated transplantation if possible. We present in this report our experience in treating two patients with extramedullary non-hematological disease in the setting of relapsed AML previously treated with HSCT, DLI, chemotherapy and radiotherapy.

Incidence of extramedullary relapse after haploidentical SCT for advanced AML/myelodysplastic syndrome

Extramedullary (EM) relapse of leukemia after allo-SCT in patients with AML/myelodysplastic syndrome has been increasingly reported. The reduced effectiveness of the GVL effect in EM sites, as compared with BM, has been suggested to underlie this problem. We retrospectively analyzed the pattern of relapse after haploidentical SCT (haplo-SCT), performed as the first or second SCT. Among 38 patients who received haplo-SCT as their first SCT, the cumulative incidences of BM and EM relapse at 3 years were 40.5 and 10.9%, respectively. Among 19 patients who received haplo-SCT as their second SCT, the cumulative incidences of BM and EM relapse were 30.9 and 31.9%, respectively. Moreover, most of the patients who underwent repeat haplo-SCT for the treatment of EM relapse had further EM relapse at other sites. Post-relapse survival did not differ significantly with different patterns of relapse. The frequent occurrence of EM relapse after haplo-SCT, particularly when performed as a second SCT, suggests that the potent GVL effect elicited by an HLA disparity also occurs preferentially in BM. Our findings emphasize the need for a treatment strategy for EM relapse that recognizes the reduced susceptibility of EM relapse to the GVL effect.

An Unusual Extramedullary Relapse of Acute Nonlymphocytic Leukemia After Allogeneic Bone Marrow Transplantation

Recurrent leukemia following allogeneic bone marrow transplantation (BMT) for acute nonlymphocytic leukemia (ANLL) continues to be a cause of morbidity and mortality. Most relapses occur within the first 6-12 months, although disease-free survival curves do not begin to plateau until 24 months posttransplant. The majority of relapses occur in the bone marrow. Extramedullary relapses usually occur in "sequestered sites," i.e., the testis and central nervous system. Although the true incidence of extramedullary relapse in "nonsequestered" sites after allogeneic BMT for ANLL is unknown, it appears that this type of relapse is distinctly unusual. The authors present a case of an unusual extramedullary relapse of ANLL in the breast at day +613 after allogeneic BMT for ANLL. In addition, we briefly review the English BMT literature and discuss the differential diagnosis of breast masses in women who survive allogeneic BMT for ANLL.

Equivalence of Intrathecal Chemotherapy and Radiotherapy as Central Nervous System Prophylaxis in Children With Acute Lymphatic Leukemia: A Pediatric Oncology Group Study

Abstract The efficacy of intrathecal (i.t.) chemoprophylaxis was compared with cranial radiotherapy plus i.t. methotrexate (MTX) in a Southwest Oncology Group (SWOG) study accessing 408 patients from September 10, 1974, to October 29, 1976. Randomization was stratified by prognostic groups (PGs) based on age and white blood cell count at diagnosis. All received induction therapy with vincristine and prednisone (Pred); maintenance therapy consisted of daily 6-mercaptopurine and weekly MTX. Consolidation for arm 1 employed cyclophosphamide and L-asparaginase followed by biweekly 5-day courses of parenteral MTX. The first dose of each course of MTX was given i.t. in triple chemoprophylaxis (MTX, hydrocortisone, and cytosine arabinoside). During maintenance, i.t. chemoprophylaxis was bimonthly and 28-day Pred “pulses” were given every 3 mo. Arm 2 i.t. chemoprophylaxis was initiated on achievement of remission, and arm 3 i.t. on treatment day 1; both continued 1 yr. Arm 4 induction included two doses of L-asparaginase. On achievement of remission, CNS prophylaxis (radiotherapy, 2400 rad plus i.t. MTX) was given. For all, therapy was discontinued after 3 yr of continuous complete remission. Survival and the incidence of extramedullary relapse were similar for the treatments employing either i.t. chemoprophylaxis or radiotherapy plus i.t. MTX upon achievement of remission. Among poor prognosis patients, the duration of complete remission was significantly better with the regimen using i.t. chemoprophylaxis as a component of consolidation therapy than with the regimen employing i.t. chemoprophylaxis early in induction or with the treatment using radiotherapy plus i.t. MTX for CNS prophylaxis. In poor prognosis patients, the initiation of i.t. chemoprophylaxis during consolidation was also associated with hematologic remissions that were significantly better than those achieved with the treatment employing early CNS chemoprophylaxis or with the regimen using radiotherapy plus i.t. MTX. Among average prognosis patients, therapy with CNS chemoprophylaxis during consolidation, as well as the regimen employing radiotherapy and i.t. MTX for CNS prophylaxis, produced hematologic remissions that were significantly longer than those obtained with the regimen using early CNS chemoprophylaxis. Hematologic remissions of good prognosis patients who received treatment with the regimen employing i.t. chemoprophylaxis during consolidation were statistically superior when compared to the regimen employing CNS radiotherapy plus i.t. MTX. This study indicates that i.t. chemoprophylaxis may be substituted for cranial radiotherapy when utilizing effective systemic regimens. Additionally, chemoprophylaxis may be reduced from 3 to 1 yr in patients with good prognostic factors.

Equivalence of intrathecal chemotherapy and radiotherapy as central nervous system prophylaxis in children with acute lymphatic leukemia: a pediatric oncology group study

The efficacy of intrathecal (i.t.) chemoprophylaxis was compared with cranial radiotherapy plus i.t. methotrexate (MTX) in a Southwest Oncology Group (SWOG) study accessing 408 patients from September 10, 1974, to October 29, 1976. Randomization was stratified by prognostic groups (PGs) based on age and white blood cell count at diagnosis. All received induction therapy with vincristine and prednisone (Pred); maintenance therapy consisted of daily 6-mercaptopurine and weekly MTX. Consolidation for arm 1 employed cyclophosphamide and L-asparaginase followed by biweekly 5-day courses of parenteral MTX. The first dose of each course of MTX was given i.t. in triple chemoprophylaxis (MTX, hydrocortisone, and cytosine arabinoside). During maintenance, i.t. chemoprophylaxis was bimonthly and 28-day Pred "pulses" were given every 3 mo. Arm 2 i.t. chemoprophylaxis was initiated on achievement of remission, and arm 3 i.t. on treatment day 1; both continued 1 yr. Arm 4 induction included two doses of L-asparaginase. On achievement of remission, CNS prophylaxis (radiotherapy, 2400 rad plus i.t. MTX) was given. For all, therapy was discontinued after 3 yr of continuous complete remission. Survival and the incidence of extramedullary relapse were similar for the treatments employing either i.t. chemoprophylaxis or radiotherapy plus i.t. MTX upon achievement of remission. Among poor prognosis patients, the duration of complete remission was significantly better with the regimen using i.t. chemoprophylaxis as a component of consolidation therapy than with the regimen employing i.t. chemoprophylaxis early in induction or with the treatment using radiotherapy plus i.t. MTX for CNS prophylaxis. In poor prognosis patients, the initiation of i.t. chemoprophylaxis during consolidation was also associated with hematologic remissions that were significantly better than those achieved with the treatment employing early CNS chemoprophylaxis or with the regimen using radiotherapy plus i.t. MTX. Among average prognosis patients, therapy with CNS chemoprophylaxis during consolidation, as well as the regimen employing radiotherapy and i.t. MTX for CNS prophylaxis, produced hematologic remissions that were significantly longer than those obtained with the regimen using early CNS chemoprophylaxis. Hematologic remissions of good prognosis patients who received treatment with the regimen employing i.t. chemoprophylaxis during consolidation were statistically superior when compared to the regimen employing CNS radiotherapy plus i.t. MTX. This study indicates that i.t. chemoprophylaxis may be substituted for cranial radiotherapy when utilizing effective systemic regimens. Additionally, chemoprophylaxis may be reduced from 3 to 1 yr in patients with good prognostic factors.