Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. @*Materials and Methods@#We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. @*Results@#Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). @*Conclusion@#In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Current Treatment Patterns and the Role of Upfront Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma: A Korean Nationwide, Multicenter Prospective Registry Study (CISL 1404) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. @*Materials and Methods@#Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. @*Results@#A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. @*Conclusion@#The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Treatment of indolent lymphoma

Treatment of indolent lymphoma has improved significantly in recent decades since the advent of rituximab (anti-CD20 monoclonal antibody). Although, some patients with limited disease can be cured with radiation therapy alone, most patients experience disease progression and recurrence during follow-up despite early initiation of treatment. Thus, watch-and-wait is still regarded the standard for asymptomatic patients. Patients with indolent lymphoma have a significant heterogeneity in terms of tumor burden, symptoms (according to anatomical sites) and the need for instant therapy. Therefore, the initiation of treatment and treatment option should be decided with a clear goal in each patient according to the need for therapy and clinical benefits with the chosen treatment. In this review, we cover the current treatment of follicular lymphoma and marginal zone lymphoma.

Extranodal NK/T cell lymphoma

Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a distinct subtype of Non-Hodgkin’s lymphoma mainly involving the nasal area. Since the entity was first recognized, treatment strategies have been evolving from anthracycline-based chemotherapy and radiotherapy to L-asparaginase containing regimens and recently immune checkpoint inhibitors. With the currently used combined chemotherapy and radiotherapy, more than 70% of patients with localized disease can be cured. L-asparaginase containing regimens have significantly improved treatment outcomes among patients with advanced disease. However, the treatment outcomes of patients with disease refractory to L-asparaginase containing regimens or who experience recurrence remain poor. In this article, we cover the current treatments for ENKTL and emerging treatment approaches.

Minor BCR-ABL1-Positive Acute Myeloid Leukemia Associated With the NPM1 Mutation and FLT3 Internal Tandem Duplication

No abstract available.

Comparison of an international scale method and a log reduction method for monitoring of early molecular response in chronic myeloid leukemia patients

No abstract available.

Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation

For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (> or = 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.

A Case of Multiple Myeloma Presenting Acute Renal Failure in a Patient with Rheumatoid Arthritis

It is known that rheumatoid arthritis (RA) patients show increased incidence of multiple myeloma (MM), despite its rarity. Only one case of MM with seronegative RA was reported in Korea, thus far. We report a case of MM with seropositive RA. The patient was a 66 year old female who had been diagnosed with seropositive RA 4 years ago. Over the last 1 month, the patient experienced general weakness and weight loss of 10 kg. It was found that her serum creatinine had increased and her urine analysis showed proteinuria. To evaluate renal failure and proteinuria, renal biopsy, bone marrow biopsy and electrophoresis were carried out. A diagnosis of myeloma cast nephropathy was made. We report this rare case of MM represented as acute renal failure during the treatment for RA, and include a review of the literature.

Patterns of Neutropenia and Risk Factors for Febrile Neutropenia of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP

Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age > or =65 yr, comorbidities, bone marrow involvement, and baseline serum albumin < or =3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.

Current routine practice and clinico-pathological characteristics associated with acute promyelocytic leukemia in Korea

BACKGROUND: Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL. METHODS: We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20-80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012. RESULTS: The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)x10(9)/L and 2.7 to 124.0 (median 54.5)x10(9)/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3-44.1) s and 29 (24-62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of >20 microg/mL. The D-dimer median value was 5,000 (686-55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2-19) d and 7 (2-13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%). CONCLUSION: Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required.

Current routine practice and clinico-pathological characteristics associated with acute promyelocytic leukemia in Korea

BACKGROUND: Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL. METHODS: We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20-80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012. RESULTS: The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)x10(9)/L and 2.7 to 124.0 (median 54.5)x10(9)/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3-44.1) s and 29 (24-62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of >20 microg/mL. The D-dimer median value was 5,000 (686-55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2-19) d and 7 (2-13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%). CONCLUSION: Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required.

Granulocytic Sarcoma in Breast after Bone Marrow Transplantation / 한국유방암학회지

Granulocytic sarcoma is a localized extramedullary solid tumor composed of immature myeloid cell and is usually associated with acute myeloid leukemia or myelodysplastic syndrome. Although it can involve any site, commonly in lymph nodes, skin, bone and soft tissue, the involvement of breast is unusual. Especially, the involvement of the breast as a pattern of relapse after bone marrow transplantation is extremely rare. We have experienced 2 cases of granulocytic sarcoma after bone marrow transplantation. One case was a 39-year-old woman with right breast mass diagnosed with granulocytic sarcoma. She had received an unrelated bone marrow transplantation due to biphenotype acute leukemia 3 years before our presentation. Another case was a 48-year-old woman with acute myeloid leukemia, who was diagnosed with granulocytic sarcoma on both breasts 8 months after allogenic bone marrow transplantation. We also discuss the clinicopathologic features of granulocytic sarcoma in breast after bone marrow transplantation.

A Case of Temporal Bone Myeloid Sarcoma / 대한이비인후과학회지

Myeloid sarcoma is a rare solid, extramedullary tumor composed of immature granulocytes, occurring in a granulocytic leukemia. In rare cases, they can represent the initial manifestation of a relapsed form in patients with acute myelogenous leukemia in remission status. There have been only a few reports of myeloid sarcoma involving the temporal bone. We report a case of facial nerve paralysis caused by temporal bone myeloid sarcoma as the presenting symptom of leukemic relapse in a 27-year-old female, who was affected by acute myelogenous leukemia.

New drugs in hematological disorders / 대한내과학회지

Modern medical oncology has introduced various anti-cancer drugs since the World War I and II. Unlike for the solid tumors, hematological malignancies had been documented some limitations for curing it with chemotherapeutic agents only. In 1960, Dr. Nowell and Dr. Hungerford had discovered elongated chromosome (Philadelphia chromosome) which has documented as a product of translocation between 9th and 22nd chromosome in the patients with chronic myeloid leukemia. In 1970s, immunochemistry technique using monoclonal antibody has spread world widely and from 1990s, flow cytometry method has been available. In appreciation of these evolutions in basic science, the treatment strategy ofhematological malignancies has changed from the chemotherapeutic agents to targeted agents. Among the targeted agents, some drugs are newly developed and others are recreated as anti-cancer drugs after long-time of discard because of their toxicities or teratogenic effects. Nowadays, we are in the middle of flood of targeted agents, for example, tyrosinekinase inhibitors, epidermal growth factor receptor blockers, farnesyl transferase inhibitors, histone deacetylase inhibitors, and etc. In 21st century, the optimal treatment of hematological malignancies should follow a tailor- made strategy according to the patient and disease itself. In the present article, some representative agents will be introduced in accordance with target diseases.

A case of donor-derived granulocytic sarcoma after allogeneic hematopoietic stem cell transplantation

The occurrence of granulocytic sarcoma as a pattern of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare. In this paper, we report a rare case of acute myeloid leukemia (AML) relapsed as a granulocytic sarcoma of the donor type. The patient was diagnosed as having AML and underwent an allo-HSCT from his matched sibling donor. Fifty-seven months after allo-HSCT, he developed granulocytic sarcomas of duodenum, jejunum, and left sterno-cleido-mastoid muscle. The bone marrow was normal with 100% donor chimerism. A Y chromosome PCR was performed on the patient's duodenum specimen as well as bone marrow aspirate in order to check the patient-origin cells. The duodenal specimen was found to contain 41.2% SRY-positive cells (from the donor). Repeat endoscopy on day 2 of chemotherapy showed that the granulocytic sarcoma had shrunk dramatically. The patient died of sepsis during the nadir state 35 days after starting salvage chemotherapy.

Concurrent Chemoradiotherapy with Weekly Paclitaxel for Locally Advanced Non-small Cell Lung Cancer

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Paclitaxel is an active agent against NSCLC and it has a radiosensitizing effect. We investigated the efficacy and toxicity of weekly paclitaxel administration along with concurrent radiotherapy for treating locally advanced and locally recurrent NSCLC. MATERIALS AND METHODS: Twenty-five previously untreated stage III or locally recurrent NSCLC patients received weekly paclitaxel (60 mg/m2) and concurrent radiotherapy. Chemotherapy was given on days 1, 8, 15 and 22. Concurrent radiotherapy at 1.5 Gy was given twice a day to a total dose of 54 Gy in 3.5 weeks. After the completion of CCRT, consolidation chemotherapy was delivered if possible. RESULTS: The overall response rate was 72% with one complete response and 17 partial responses. The median overall survival was 16 months with a 2 year survival rate and a 5 year survival rate of 38% and 24%, respectively. The rate of grade > 3 radiation pneumonitis was 16% (4 patients) and 2 patients were died from the pneumonitis. The rate of grade 3 radiation esophagitis was 12% (3 patients) and the hematologic toxicities were not significant. CONCLUSION: Weekly paclitaxel with concurrent radiotherapy is effective for treating locally advanced and locally recurrent NSCLC, but radiation pneumonitis is the major toxicity and this is potentially fatal.

Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia

BACKGROUND: Acute leukemias co-expressing myeloid and lymphoid antigens but does not meet the criteria for biphenotypic acute leukemia (BAL) is common, however its clinical significance is not fully defined. METHODS: In this study, clinical features of 68 co-expressing (myeloid and lymphoid) acute leukemias diagnosed between January 2000 and December 2006 were studied and compared with those of a control group of patients (pure AML or ALL). RESULTS: Age, gender, initial Lactate dehydrogenase (LDH) level and cytogenetics were not different between the co-expressing group and the control group. But, the initial bone marrow blast percent was significantly higher in the co-expressing group (70% vs. 54.5%, P=0.003). Fifty five percent (16/29) of ALL and 30% (52/172) of AML patients showed myeloid and lymphoid markers concomitantly. The lymphoid antigen positive AML (Ly+AML) patients showed significantly shorter survival rates than pure AML patients (4 year survival rate, 17.6% vs. 45.6%, P=0.002). However hematopoietic stem cell transplantation (HST) abrogated the difference (4 year survival rate, 54.7% vs. 50.6%, P=0.894). In ALL patients, survival rate was not affected by myeloid antigen co-expression (4 year survival rate 26.1% vs. 20%, P=0.954). CONCLUSION: Co-expression of lymphoid markers in AML should be regarded as a poor prognostic factor and more aggressive treatment such as HST should be considered.

A Case Report of Helicobacter Pylori Negative Gastric MALT Lymphoma with Monoclonal Gammopathy

Lymphomas of mucosa-associated lymphoid tissue (MALT) comprise 7% of all newly diagnosed non-Hodgkin's lymphomas. Helicobacter pylori (H. pylori) negative gastric MALT lymphomas account for 28 to 45% of gastric MALT lymphomas. H. pylori infection has a close relationship with most gastric low-grade B cell lymphomas of the MALT type. Monoclonal gammopathy can be seen in 36% of the patients and negatively associated with responses to eradication of H. pylori in gastric MALT lymphoma. Here, we describe a case of H. pylori negative MALT lymphoma that arose from the stomach with massive plasmacytic differentiation mimicking an extramedullary plasmacytoma with monoclonal gammopathy, and that was cured by total gastrectomy, chemotherapy and radiotherapy.

Difference in Viability of CD34+Cells in Cryopreserved Cord Blood According to Evaluation Methods

BACKGROUND: On performing umbilical cord blood (UCB) transplantation, faster engraftment may lead better clinical outcome. Because transplanted viable cell count in UCB is related to the engraftment, accurate evaluation of viability of CD34+cells in cryopreserved UCB has clinical implication. We examined the difference in viability of cells in cryopreserved UCB according to the duration of cryopreservation and different methods. METHODS: A total of 60 UCB samples which were cryopreserved for 1 to 4 years were used in this study. Viability of cryopreserved cells were examined with trypan blue exclusion assay, DNA contents analysis, caspase-3 activation test, intracellular esterase activity and Annexin-V/PI staining. RESULTS: After thawing the cryopreserved UCB, 89% of the total MNCs and 84% of CD34+cells were viable as identified by trypan blue exclusion assay. In the CD34+cell population, the cell death rate was found to be 47% by Annexin-V/PI staining and less than 5% by DNA contents analysis. However, cspase-3 activity failed to document apoptosis. The intracellular esterase activity test also showed a cell death rate of about 10~20% at 2, 4, and 6 hours after thawing. CONCLUSION: Viable cells in UCB should be measured by several compensatory techniques rather than a single method. Discordance among Annexin-V/PI staining versus trypan blue exclusion, DNA contents analysis, and the caspase-3 activation test or intracellular esterase activity should be clarified in order to apply these techniques for actual cord blood transplantation.

A case of primary small-cell carcinoma of the larynx / 대한내과학회지

Small-cell carcinoma is predominantly found in the lungs and only about 5% of small-cell carcinoma cases are extrapulmonary in origin. Extrapulmonary small-cell carcinomas are commonly found in the esophagus, pancreas, skin, uterus, breast, and prostate. Small-cell carcinoma of the head and neck is extremely rare. Although both pulmonary and extrapulmonary small-cell carcinomas usually show a good initial response to chemotherapy, the prognosis is dismal. We report a case of supraglottic small-cell carcinoma with ipsilateral cervical lymph node metastasis in a 69-year-old man. The patient was treated with concurrent platinum-based chemoradiotherapy and remains in complete remission with an excellent performance status.