[Efficacy and side effect analysis of paclitaxel liposome for neoadjuvant chemotherapy in locally advanced cervical cancer].

Objective: To investigate the efficacy and side effect of paclitaxel liposome for neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer. Methods: This study were included 265 cervical cancer patients staging Ⅰb2 and Ⅱa2 who underwent paclitaxel-platinum NACT followed by radical surgery from June 2008 to December 2016 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. All patients were classified into two groups with 106 patients in paclitaxel liposome group and 159 patients in traditional paclitaxel group. The difference in clinicopathologic characteristics, efficacy and side effect were analyzed retrospectively between the two groups. Results: (1) Clinicopathologic characteristics: there were no significant difference in clinicopathologic characteristics between the two groups, including age, body mass index, clinical stage, pathological histology, cycles of NACT, combined platinum regimen, lymph-vascular space invasion, lymph node metastasis, deep stromal invasion, and postoperative adjuvant therapy (all P>0.05). (2) Efficacy: after NACT, the overall response occurred in 90 (15 complete response plus 75 partial response) of 106 cases in the paclitaxel liposome group versus 131 (21 complete response plus 110 partial response) of 159 cases in the traditional paclitaxel group without statistical significance (84.9% vs 82.4%; χ(2)=0.291, P=0.590). A total of 248 patients received surgery after NACT and were evaluable in survival. The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of these patients was 85.1% and 88.2%. The 5-year RFS rate in the paclitaxel liposome group was 85.9% compared with 85.2% in the traditional paclitaxel group, while the corresponding 5-year OS rate was 88.5% and 88.7%, respectively. There was no statistically significant difference in efficacy between the two groups (P=0.968, P=0.797). (3) Side effect: the incidence of allergic reaction between the paclitaxel liposome group and the traditional paclitaxel group was 0 versus 1.9% (3/159) without statistical significance (P=0.277). But the incidence of neurotoxicity in the paclitaxel liposome group significantly decreased compared with the traditional paclitaxel group (6.6% vs 15.7%, P<0.05), as well as the incidence of alopecia (67.9% vs 79.2%, P<0.05) and myalgia (17.9% vs 28.9%, P<0.05). However, significant differences were not found in terms of hematological toxicity, gastrointestinal reaction, and hepatic function damage (P>0.05). Conclusion: In paclitaxel-platinum NACT of local advanced cervical cancer, paclitaxel liposome can achieve similar efficacy compared with traditional paclitaxel, but paclitaxel liposome is helpful in decreasing the toxicity of neurotoxicity, alopecia and myalgia.

Systemic lupus erythematosus is a risk factor for cancer: a nationwide population-based study in Korea.

OBJECTIVE: Specific differences in cancer risk have been observed between systemic lupus erythematosus patients and the general population. Although meta-analyses have estimated cancer incidence in systemic lupus erythematosus patients, results have been inconclusive. Hence, we aimed to assess malignancy risk in systemic lupus erythematosus patients, compared to the risk in the general population. METHODS: Systemic lupus erythematosus patients ( n = 21,016; mean age 41.67 ± 13.14 years; female 90.22%) were selected from the Korean National Health Insurance Service database between 2008 and 2014. Age- and sex-matched controls were randomly sampled in a 5:1 ratio ( n = 105,080). RESULTS: During the 7 years of follow up, malignancy was detected in 763 (3.63%) systemic lupus erythematosus patients and 2667 (2.54%) controls. Systemic lupus erythematosus patients had a higher risk of malignancy than controls (odds ratio 1.44; 95% confidence interval 1.327-1.559), after multivariate adjustment. Systemic lupus erythematosus patients had a higher odds ratio for developing cervical, thyroid, ovarian, and oral cancer, as well as lymphoma, leukemia, and multiple myeloma than controls. Based on subgroup analysis, male systemic lupus erythematosus patients and patients younger than 40 years showed the highest lymphoma risk. CONCLUSIONS: Systemic lupus erythematosus might be an independent risk factor for cancer. Therefore, the importance of cancer screening programs should be emphasized in systemic lupus erythematosus patients. Our study is the first large nationwide cohort study for evaluating the risk of cancer in systemic lupus erythematosus patients.

[The clinicopathological features and risk factors of recurrence in patients with mucinous borderline ovarian tumors].

Objective: To investigate the clinicopathological features and risk factors in patients with mucinous borderline ovarian tumors (MBOT). Methods: From 1999 to 2006, 66 MBOT patients in our hospital with more than ten-year follow-up were enrolled retrospectively. They were re-classified according to the literature. The clinicopathological features of different subgroups, including age, preoperative serum tumor markers, surgical methods, pathological features, surgical pathology staging, as well as the risk factors of recurrence and survival were analyzed. Results: Median age was 39 years in 66 patients. Before the surgery, 33.3% (20/60) patients had elevated CA125 and 51.7% (30/58) had elevated CA199. The accurate rate for fast frozen pathology of resected specimen was 73.4%. 21 patients underwent conservative surgery and 45 patients underwent extensive surgery. 57 patients underwent comprehensive operation and 43 cases (75.4%) resulted in stage Ⅰ. 48 of the 66 patients (72.7%) had intestinal-type tumors (IMBT) and 18 patients (27.3%) had endocervical-like tumors (EMBT). The median follow-up was 150 months. Eight recurrences (12.1%) were identified. The mean time between surgery to the initial recurrence was 26.4 months (13 to 50 months). Recurrence rate of IMBT was higher than that of EMBT (14.6% versus 5.6%) with no significance (P>0.05). All patients with pseudomyxoma had disease recurrence. Recurrence rate of stage Ⅲ patients was significantly higher than that of stage Ⅰ patients (33.3% versus 9.3%, P<0.05). During the follow-up period, tumor-related death occurred in 2 cases with a 10-year survival rate of 95.4%. Kaplan-Meier method and Log Rank analysis showed that clinical staging and peritonealmyxoma were adverse prognostic factors (P<0.05). Although the recurrence rate of patients undergoing conservative surgery was higher than that of patients with extensive surgery (23.8% versus 6.7%, P=0.047), the overall survival was almost the same between these two groups (P>0.05). Conclusions: MBOT patients have relatively good prognosis. IMBT are more common than EMBT subtypes, but recurrence rate and patient survival were almost the same between these two groups. Patients with pseudomyxoma was more likely to have disease recurrence. Patients who underwent conservative surgery resulted in higher recurrence rate but did not affect the overall survival of patient. Pseudomyxoma and clinical staging were adverse prognostic factors in MBOT patients.

Prognostic impact of hyponatraemia in patients with colorectal cancer.

AIM: Hyponatraemia is a common in surgical practice, but its clinical impact in patients with colorectal cancer has not been evaluated. METHOD: We retrospectively assessed 2944 patients who had been admitted to Chonnam National University Hwasun Hospital, Korea with a diagnosis of colorectal cancer. In order to determine the relationship between the serum sodium level and 3-year mortality, we categorized the patients as having normonatraemia (135-147 mEq/l), or mild (130-134 mEq/l), moderate (125-129 mEq/l) or severe hyponatraemia (< 125 mEq/l). RESULTS: Hyponatraemia, defined as a serum sodium level of < 135 mEq/l, was evident in 27.6% of patients during hospitalization. Declining serum sodium levels were associated with increasing age, a higher number of comorbidities, a more advanced TNM stage and worsening biochemical parameters. In a multivariate Cox-proportional regression analysis, the mortality risk was correlated with the severity of hyponatraemia [hazard ratio (HR) 1.65, 95% CI 1.38-1.96; HR 2.24, 95% CI 1.69-2.98; HR 2.20, 95% CI 1.25-3.90, for patients with mild, moderate, and severe hyponatraemia, respectively, compared with patients with normonatraemia]. An independent association between hyponatraemia and long-term mortality was sustained among various subpopulations and patients with persistent hyponatraemia had a worse prognosis than those with hyponatraemia that resolved. CONCLUSION: A substantial proportion of patients developed hyponatraemia during hospitalization, and the long-term mortality risk increased even in mild cases of hyponatraemia. Hyponatraemia should be considered as an important prognostic factor in colorectal cancer.

Glucose-6-phosphate-dehydrogenase deficiency and haematopoietic stem cell transplantation in Chinese patients.

Deficiency in glucose-6-phosphate dehydrogenase (G6PD), an X-linked recessive red cell enzymopathy, is endemic in Southern Chinese. Universal screening of newborn is done in Hong Kong, Taiwan and Singapore, among other places. In Hong Kong, 4.8% of males are affected and seven common G6PD alleles account for over 99% of all defects. Male hemizygotes suffer from severe deficiency, while female heterozygotes may also be affected. Deficiency of G6PD may affect haematopoietic stem cell transplantation (HSCT) recipients and donors, before and after HSCT. Female patients with clonal erythropoiesis (eg myelodysplasia/myeloproliferative diseases) will have the male population incidence of G6PD. Quantitative enzyme level screening is prudent for donors and recipients, and should be repeated after engraftment. Cotrimoxazole prophylaxis should be avoided in known male and female carriers, including those with low-normal G6PD enzyme levels. Our experience suggested that G6PD-deficient marrow, stem cell and cord blood donor units have no engraftment problems. Post-engraftment G6PD levels correlate with those in donors. An acquired change in G6PD status may serve as a surrogate marker for engraftment. For female heterozygote donors with normal G6PD levels, skewing of lyonized X-chromosome ratio during engraftment may result in over-expression of the deficient allele. This can result in unexpected significant G6PD deficiency. Hence, a repeat G6PD screening at stable engraftment is recommended, especially before commencement of oxidative medications.

Serial analysis of JAK2 mutation in a patient who developed essential thrombocythemia after orthotopic liver transplantation.

A 52-year-old man developed essential thrombocythemia (ET) with JAK2 V617F mutation after orthotopic liver transplantation (OLT). Retrospective analysis showed that, despite a low platelet count, the JAK2 mutation was already found at presentation 14 months before OLT. The high platelet count that would have been typical of ET might be masked by the cirrhosis-related hypersplenism. Thrombocythemia became obvious after OLT. The patient subsequently developed blastic transformation 12 months afterward, a process probably accelerated by the immunosuppression required for the OLT.

Der(8)t(1;8) in myeloblastic transformation of ET with hydroxyurea as the sole prior treatment.

We described a patient with ET that evolved into MF and then subsequently developed myeloblastic transformation. A novel derivative chromosome der(8)t(1;8) was identified in the AML phase. The only prior treatment had been hydroxyurea. We hypothesized that AML in this case resulted from a complex pre-disposition by the natural progression of ET, prolonged use of HU, and the prior evolution into MF. The leukemogenic risk of HU is critically appraised.

Eosinophilic leukemic transformation in polycythemia rubra vera (PRV).

We report a rare case of eosinophilic leukemia transformation in a patient with polycythemia rubra vera on hydroxycarbamide (hydroxyurea) therapy only. Cytogenetic study showed complex abnormalities including -5, -7, +8, suggestive of a secondary leukemia. The leukemogenic risk of hydroxycarbamide, a ribonucleoside reductase, and the risk of natural leukemic transformation of polycythemia rubra vera is discussed in the context of previous PVSG studies.

Potential role for platelet apheresis for post-liver transplant thrombocytosis complicating portal vein thrombosis.

Except for patients with underlying myeloproliferative diseases (MPD), thrombocytosis is rarely encountered in cirrhotic patients after liver transplantation. Although the long-term control of primary thrombocytosis is important for the prevention of graft thrombosis in MPD patients, the threshold for intervention and best mode for the control of persistent reactive thrombocytosis after liver transplantation is unclear. We present two patients with extreme reactive thrombocytosis (over 1,000 x 10(9)/l) due to intra-abdominal sepsis after liver transplantation. Furthermore, both patients suffered from bleeding problems as well as ongoing venous thrombosis of the graft. Rapid control of the platelet count was achieved using platelet apheresis. The use of cell separation procedures may be a relatively rapid, reversible, and reasonably safe way to control platelet counts peri-operatively in liver transplant recipients.

Pathogenesis of jumping translocations: a molecular cytogenetics study.

BACKGROUND/AIMS: Jumping translocations are rare cytogenetic aberrations in haematological malignancies, the pathogenesis of which remains to be fully characterised. We investigated the mechanism of formation of jumping translocations in a case of adult common acute lymphoblastic leukaemia (ALL) positive for the Ph translocation. METHODS: Interphase and metaphase fluorescence in situ hybridisation (FISH) was performed using several probe systems. Results were correlated with findings on conventional cytogenetics. Granulocytes, T-cells and leukaemic B-cells in peripheral blood were sorted by immunomagnetic method and the terminal restriction fragment (TRF) length of these cellular populations was determined by Southern blot analysis. RESULTS: Duplicated BCR-ABL fusion signals were found on a dic(14;22)der(22)t(9;22) chromosome. Clonal jumping translocations, existing as evolutionary changes, involved the donor chromosomal segment distal to 1q12 jumping onto the telomere ends of 11q, 15p, 19p and 20p. Telomere length was decreased in the neoplastic B-cell population and contributed to the formation of the dicentric chromosome that showed absence of telomere repeats at fusion ends. Subsequent pericentromeric heterochromatin decondensation of chromosome 1q occurred, and this donor segment was randomly fused to the shortened telomere ends of non-homologous chromosomes. CONCLUSIONS: Both telomere shortening and pericentromeric heterochromatin decondensation contribute to the formation of jumping translocations, which is most probably a multi-stage process.

Transformation of diffuse large B-cell lymphoma into pre-B acute lymphoblastic leukemia: clinicopathologic features and clonal relationship.

A patient with fibrosing alveolitis developed a diffuse large B-cell (DLBC) lymphoma that expressed CD20 and CD30. After an initial response, the lymphoma relapsed and was salvaged with further chemotherapy. After another remission of 3 years, a pre-B-cell acute lymphoblastic leukemia (ALL), which expressed CD10, CD19, CD22, CD79a, CD34 and terminal deoxyribonucleotidyl transferase, developed and led to death. Molecular analysis of the immunoglobulin heavy-chain gene showed that the initial lymphoma and its relapse were clonally related. At leukemic relapse, 2 clones related to the initial and relapsed lymphoma clones were present. DLBC lymphomas arise from post-follicle center B cells, whereas ALL arises from pregerminal B cells. Therefore, a direct transformation of DLBC lymphoma to ALL appears unlikely. The overall features suggest instead separate lymphoma and leukemic evolution from a common mutated B-cell precursor rather than transformation of DLBC lymphoma to ALL.

Bone marrow transplantation for therapy-related acute myeloid leukemia in congenital retinoblastoma associated with 13q deletion syndrome.

Children with constitutional deletion of the long arm of chromosome 13 are at risk for retinoblastoma (RB) due to loss of the RB tumor suppressor gene. The prognosis is poor since the tumors are often bilateral, aggressive, and recurrent and the patients often harbor other congenital abnormalities. One further complication is that of therapy-related malignancies later in life. We report a case of allogeneic stem cell transplantation for therapy-related acute myeloid leukemia in an 8-year-old girl after multimodality treatment for refractory bilateral relapsing RB, with excellent outcome in both the ophthalmic and marrow disease.

Chronic myeloid leukemia in an adolescent with Ollier's disease after intensive X-ray exposure.

We report a 19-year-old man with Ollier's disease with multiple orthopedic procedures performed for leg length discrepancy; who developed chronic myeloid leukemia presenting with intramuscular hematoma. His symptoms resolved with cytoreductive treatment by hydroxyurea. Cytogenetic and molecular investigations showed a complex Philadelphia translocation t(9;22;13) (q34;q11.2;q12), with predominance of ela2 BCR/ABL splicing and deletion of reciprocal der(9) ABL/BCR locus, all suggesting poor prognosis. The cumulative X-ray exposure from repeated operations from the age of 7 to 12 years was estimated to be around 16 mSv, approximately the dose of 720 chest X rays. Literature review showed two other cases of leukemia occurring in patients with multiple enchondromatosis. Although the development of CML in this young patient might be related partly to genetic defects, the repeated radiation exposure, especially at young age and directly on the marrow tissue in the long bones, might also be an important pathogenetic factor.

Treatment of postrenal transplantation lymphoproliferative disease manifesting as plasmacytoma with nonmyeloablative hematopoietic stem cell transplantation from the same kidney donor.

Posttransplantation lymphoproliferative disease (PTLD) presenting as an Epstein-Barr-virus (EBV)-related nasal plasmacytoma developed in a renal-allograft recipient 13 years after transplantation. Systemic dissemination occurred despite immunosuppression withdrawal, surgery, irradiation, and chemotherapy. A nonmyeloablative hematopoietic-stem-cell-transplantation (HSCT) with peripheral blood HSC from the kidney donor was performed. With the onset of graft-versus-host disease, resolution of the systemic disease was demonstrated clinically and molecularly by serial quantification of plasma EBV-DNA. Isolated relapse occurred in the central nervous system (CNS), a known tumour sanctuary site, ultimately leading to death. Nonmyeloablative HSCT might be considered a cellular therapy for PTLD, but possible CNS relapse must be effectively tackled.

The occurrence of Philadelphia chromosome (Ph) negative leukemia after hematopoietic stem cell transplantation for Ph positive chronic myeloid leukemia: implications for disease monitoring and treatment.

Chronic myeloid leukemia (CML) is a clonal neoplastic disorder, characterized by t(9;22)(q34;q11) that results in the formation of the Philadelphia chromosome (Ph) and the BCR/ABL fusion gene. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for CML. Much of its therapeutic efficacy is attributed to a graft-versus-leukemia (GVL) effect exerted by donor-derived lymphoid cells against the Ph positive (Ph+) clone. Post-HSCT monitoring by cytogenetic and molecular detection of the Ph+ clone is necessary, so that pre-emptive immunologic or pharmacologic treatment may be administered at an early stage of relapse. However, under rare circumstances a second Ph negative (Ph-) leukemia may evolve post-HSCT. The pathogenetic possibilities included leukemia arising from donor-derived hematopoietic stem cells (HSCs), or transformation of residual recipient-derived Ph- HSCs that have survived the conditioning chemotherapy and radiotherapy. Recipient-derived Ph- leukemia may be related to genetic alterations that precede the onset of CML, or myelotoxic effects of the HSCT conditioning regimen. The diagnosis of Ph- relapses requires detailed investigations by conventional karyotyping, fluorescence in-situ hybridization (FISH), and molecular analysis; as well as chimerism studies that help to document the donor or recipient origin of the leukemia. Although uncommonly reported in the past, Ph- relapses may in fact be more frequent if leukemic relapses post-HSCT are more thoroughly evaluated with these investigations. The recognition of Ph- relapses are important in several ways. Ph- relapses cannot be identified by monitoring investigations targeting the Ph+ clone, so that the early detection of Ph- leukemia is usually not possible. Furthermore, Ph- relapses will not respond to therapeutic strategies effective against the Ph+ CML clone.

Derivative chromosome 9 deletions in chronic myeloid leukaemia: interpretation of atypical D-FISH pattern.

BACKGROUND/AIMS: New molecular cytogenetic techniques are increasingly applied as a routine investigative tool in haematological malignancies, both at diagnosis and subsequent monitoring. This report describes the interpretation of atypical signal patterns encountered using BCR-ABL dual colour dual fusion fluorescence in situ hybridisation (D-FISH) translocation probes in chronic myeloid leukaemia (CML). METHODS: Interphase FISH experiments were carried out using BCR-ABL D-FISH probes in 46 patients with CML at diagnosis and during subsequent disease monitoring. Atypical hybridisation signal patterns were characterised by molecular cytogenetic techniques and correlated with conventional karyotyping. RESULTS: Two patients showed atypical interphase D-FISH patterns with one orange, one green, and one fusion (1O1G1F) signal. The presence of BCR-ABL gene fusion was documented by a dual colour single fusion (S-FISH) probe. The submicroscopic deletion of the ABL-BCR fusion gene on the derivative chromosome 9 in these cases was subsequently characterised by metaphase FISH on relocated G banded metaphases. CONCLUSIONS: Atypical interphase D-FISH patterns should not be interpreted in isolation and should be considered in conjunction with other cytogenetic or molecular genetic investigations.

Poor engraftment after allogeneic bone marrow transplantation: role of chimerism analysis in treatment and outcome.

We analyzed the clinical course and risk factors of 18 patients with poor engraftment after allogeneic bone marrow transplantation (BMT), defined as absolute neutrophil count below 0.1 x 10(9)/l 28 days post-BMT. Significant risks associated with non-engraftment included HLA one antigen mismatch, BMT from matched unrelated donor, and a low dose of colony-forming units-granulocyte-macrophage (<10(4)/kg). Examined by a semiquantitative analysis of polymorphic microsatellite markers, donor DNA chimerism on day 28 was found to be predictive of treatment outcome. Seven patients had detectable donor DNA, varying from 43 to 100%. Five of them responded to granulocyte colony-stimulating factor (G-CSF) and achieved engraftment. Two were given further infusions of peripheral blood hematopoietic stem cells (PBSC) from the same donors, resulting in engraftment in one of them. Eleven patients had no detectable donor DNA, and none responded to G-CSF. Autologous regeneration occurred in six of these patients, four after infusion of backup marrow and two spontaneously. The remaining five patients died despite the administration of PBSC from the same or different donors. Regular monitoring of donor DNA chimerism is useful in the management of patients at high risk of poor engraftment.