Traditional Chinese medicine on treating myelosuppression after chemotherapy: A protocol for systematic review and meta-analysis.

BACKGROUND: Myelosuppression after chemotherapy is a common adverse reaction in the process of chemotherapy, mainly manifested as anemia, increased risk of bleeding, infection, the results seriously affect the quality of life and prognosis of patients, become the main cause of death. Since ancient times, traditional Chinese medicine (TCM) has been widely used in East Asia (such as China, Japan, South Korea) in the clinical treatment of bone marrow suppression after chemotherapy, which plays the role of synergism, toxicity reduction, immune regulation, and gradually developed into an indispensable role. Therefore, the purpose of this study was to use a network meta-analysis to evaluate the evidence that traditional Chinese medicine is related to the efficacy and safety of chemotherapy-induced myelosuppression. METHODS: This study will search the following Chinese and English databases electronically: 4 Chinese literature databases, including China biology and medicine database, China National Knowledge Infrastructure, VIP, and Wan fang database, and 3 British literature databases including PubMed, EMBASE, and Cochrane Library. The search keywords were (traditional Chinese medicine or medicinal plants or extracts of traditional Chinese medicine or traditional Chinese medicine formula or preparation) and (myelosuppression after chemotherapy) and (randomized controlled trials) (RCTs). The search time limit is set to December 2020, and Chinese and English languages will be included. The included subjects must be diagnosed with myelosuppression after chemotherapy and RCTs should be conducted at the same time. The main outcome was elevated hemoglobin, platelets, leukocytes, and neutrophils. The secondary results were reticulocyte absolute value, reticulocyte percentage, low-fluorescence reticulocyte red, medium-fluorescent reticulocyte red, and high-fluorescence reticulocyte red. We will conduct a risk and quality assessment of the included studies using the Cochrane tool, and carefully calculate data synthesis after meta-analysis using Rev Man software (version 5.3.5) and R software (version 3.6.1). RESULTS: The study is aim to evaluate the efficacy and safety of the treatment that traditional Chinese medicine for myelosuppression after chemotherapy. CONCLUSION: This study of the meta-analysis could provide evidence for clinicians and help patients to make a better choice. INPLASY REGISTRATION NUMBER: INPLASY2020120097.

Analysis of the long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head.

OBJECTIVE: to investigate the safety and long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head. METHOD: a total of 76 patients with non-traumatic osteonecrosis of the femoral head were admitted to our hospital from February 2012 to November 2014 and included in the study. All the patients were treated by core decompression with synthetic calcium-sulfate bone grafting. After treatment, the patients were followed-up for 12 months. The operation time, intraoperative blood loss, and perioperative complications were also recorded intraoperatively to evaluate the clinical efficacy and safety. The preoperative and postoperative pain scores measured by visual analogy score (VAS) were also recorded and compared. RESULTS: all of the 76 patients were successfully operated and included in the study. The mean operation time was 34.6±14.2 min, and the intraoperative blood loss was 23.6±8.9 mL. The patients hip functions were assessed on the basis of the Harris hip score, 3 and 12 months after operation. The excellent rates 3 and 12 months after operation were significantly higher than those before operation (P<0.05). The imaging stabilities of the hip joints 3 and 12 months after operation were significantly higher than those before operation (P<0.05). The patient postoperative pain scores (VAS score) gradually decreased. The VAS scores 12 months after operation were significantly lower than those before operation (P<0.05). CONCLUSION: the long-term efficacy of core decompression with synthetic calcium-sulfate bone grafting on non-traumatic osteonecrosis of the femoral head is good and accompanied with significantly improved postoperative joint functions.

Treatment of bone marrow edema of the talus with pulsed electromagnetic fields: outcomes in six patients.

BACKGROUND: Bone marrow edema (BME) of the talus is a rare, mostly self-limiting cause of foot and ankle pain. We sought to investigate in patients with idiopathic BME of the talus the effectiveness of pulsed electromagnetic fields and to determine the effect of this therapy on magnetic resonance imaging findings. METHODS: Six patients with BME of the talus confirmed by magnetic resonance imaging were enrolled. Pain was quantified with a visual analog scale from 0 (no pain) to 10 (the worst pain imaginable). The clinical outcome was assessed using the American Orthopaedic Foot and Ankle Society scoring system. Treatment consisted of pulsed electromagnetic field stimulation 8 h/d for 30 days. The device used generated pulses 1.3 milliseconds in duration, with a frequency of 75 Hz and a mean ± SD induced electric field of 3.5 ± 0.5 mV. RESULTS: The mean American Orthopaedic Foot and Ankle Society score improved from 59.4 (range, 40-66) before treatment to 94 (range, 80-100) at the last follow-up. The visual analog scale score decreased significantly from 5.6 (range, 4-7) before treatment to 1 (range, 0-2) at the last follow-up. Magnetic resonance imaging showed that BME improved after 1 month of treatment and resolved completely within 3 months in 5 patients, with normal signal intensity and no signs of progression to avascular necrosis. CONCLUSIONS: A significant reduction in BME area was associated with a significant decrease in pain within 3 months of beginning treatment.

Hyperbaric oxygen therapy for transient bone marrow oedema syndrome of the hip.

Transient bone marrow oedema syndrome of the proximal femur is characterized by acute, progressive pain in the hip that is increased by weight-bearing. Treatment includes restricted weight-bearing and analgesic medication. A prospective, randomized study was performed to compare two groups of patients affected by bone marrow oedema syndrome of the femoral head. 20 patients received pharmacological and hyperbaric oxygen therapy, and a control group of 21 patients received pharmacological therapy alone. The overall average WOMAC score at 3 months was significantly higher (p<0.001) for the hyperbaric oxygen group (70.8 points) compared with the control group (56.4 points). Magnetic Resonance Imaging at 3 months showed resolution of bone marrow oedema in 55.0% of the patients treated with hyperbaric oxygen compared with 28% in the control group. Hyperbaric oxygen therapy appears to be effective in treating transient bone marrow oedema syndrome, resulting in an accelerated recovery of hip function compared to pharmacological therapy alone.

Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes.

Many patients with bone marrow failure syndromes need frequent transfusions of red blood cells, and most of them eventually suffer from organ dysfunction induced by excessively accumulated iron. The only way to treat transfusion-induced iron overload is iron chelating therapy. However, most patients have not been treated effectively because daily/continuous administration of deferoxamine is difficult for outpatients. Recently, a novel oral iron chelator, deferasirox, has been developed, and introduction of the drug may help many patients benefit from iron chelation therapy. In this review, we will discuss the current status of iron overload in transfusion-dependent patients, and the development of Japanese guidelines for the treatment of iron overload in Japan, which were established by the National Research Group on Idiopathic Bone Marrow Failure Syndromes in Japan.

Bone marrow oedema and aseptic osteonecrosis in children and adolescents with acute lymphoblastic leukaemia or non-Hodgkin-lymphoma treated with hyperbaric-oxygen-therapy (HBO): an approach to cure? -- BME/AON and hyperbaric oxygen therapy as a treatment modality.

BACKGROUND: There is a striking need for additional therapies of bone marrow oedema (BME) and aseptic osteonecrosis (AON) in paediatric oncology patients. Hyperbaric oxygenation (HBO) therapy used in the treatment of osteoradionecrosis is demonstrated effectiveness. Aim of this retrospective analysis was to investigate whether HBO-therapy might lead to subjective as well as objective effects in the treatment of BME and/or AON in paediatric oncology patients with acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Between 11/1988 and 01/2001 27/291 (9.3 %) patients with ALL or NHL were diagnosed with a BME and/or AON in the Clinic for Paediatric Oncology, Haematology, and Immunology at University of Dusseldorf. 19/27 patients were submitted to HBO-therapy. Patients received average 45 HBO-treatments per patient (min. 13, max. 80 treatments). The affected regions were re-evaluated with MRI for radiological extent of lesions every 3 months. Pain in its intensity and localisation was serially recorded during HBO-therapy as key symptom in 11 of 19 patients. RESULTS: 27 patients (15 females, 12 males; mean age at diagnosis of malignancy 8.2 +/- 4.7 (SD) years, range 7 months to 16 years) presented with 138 lesions. 133/138 lesions were localised in the lower extremities. At diagnosis of BME and/or AON, 78/133 lesions were shown in females and 55/133 lesions in male. Girls < 10 years predominantly presented BME (33 BME vs. 6 AON), girls aged > 10 years predominantly offered AON (28 AON vs. 11 BME). BME was more often exhibited in boys < 10 years (34 BME vs. 10 AON) and rarely in boys > 10 years (4 BME vs. 6 AON). 11 patients treated with HBO-therapy were serially evaluated for pain intensity throughout their HBO-therapy courses by visual analogue scale (VAS) assessment. During the first 15 treatment courses the HBO-therapy a clear-cut reduction of pain was observed. The mean pain score before the first HBO-treatment unit was 2.4 +/- 2.7 (X +/- SD), decreased before the fifth to 1.6 +/- 1.7 and prior to the 35 (th) and 40 (th) HBO treatment to 0. Girls < 10 years treated with HBO showed an increase of BME (31 --> 46) and declining AON numbers (6 --> 2). Girls > 10 years with and without HBO-therapy showed decrease of BME lesions (7 --> 4 vs. 4 --> 0), whereas AON increased in the HBO-treated group (28 --> 29) as well as the non-treated group (0 --> 4). Males < 10 years showed an increase in BME lesion numbers despite HBO intervention (24 --> 26). The AON lesion numbers dropped in parallel (6 --> 3). Male patients not treated with HBO showed constant numbers of BME (11-->11) and a decreased numbers of AON (4 --> 2). All differences are statistically not significant. CONCLUSIONS: Children and adolescents diagnosed with ALL or NHL have a risk for accruement of BME and/or AON irrespective of the age, with an almost exclusive involvement of the lower extremities. Lesions of pedal bones and ankle joints predominantly affect children < 10 years. Lesions of knee and hip joints predominantly affect children > 10 years. In children < 10 years of age we demonstrate declining AON numbers and conversion of AON to BME thereby implicating possible beneficial effect of HBO in such patients. HBO failed to show beneficial effect on BME whether by preventing new lesions or by improving existent lesions in children > 10 years.

First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial).

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26-56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m(-2) - doxorubicin (D) 75 mg m(-2) cycle 1, C: 3 g m(-2) - D: 75 mg m(-2) cycle 2, C: 3 g m(-2) - D: 75 mg m(-2) - 5 FU 2500 mg m(-2) cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4-1.04) and 0.96 (range 0.25-1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% +/- 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3-9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% +/- 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome.

The true cost of bone marrow transplantation.

Bone marrow transplantation is an example of a highly technical therapy that offers hope to patients with bone marrow failure or various malignancies. Bone marrow transplantation is much more costly "up-front" but perhaps not more costly long-term than alternative therapies. Although economic analyses appear relatively simple, interpretation and use can be problematic. Several economic analyses have identified complications that occur frequently and affect the reported cost-effectiveness of high-dose chemotherapy. Efforts to reduce the cost of bone marrow transplantation have focused on new strategies to more effectively control these complications. The introduction of new technologies to speed engraftment, to improve patient selection methods, and the shifting of care to outpatient settings all have resulted in significant reductions in duration of hospital stay, treatment-related mortality, and costs. More studies of long-term outcomes are needed for transplant and nontransplant treatment options to guide present and future applications of this treatment option.

A phase II study of cyclophosphamide followed by PIXY321 as a means of mobilizing peripheral blood hematopoietic progenitor cells.

Fourteen patients with stage II-IV breast cancer were enrolled in a phase II study of cyclophosphamide followed by PIXY321 as a means of mobilizing peripheral blood progenitor cells (PBPC). All 14 women tolerated PIXY321 well, with the predominant toxicities being erythema at the injection site, fever, and arthralgias. A median of two aphereses yielded a mean of 1.3 x 10(8) mononuclear cells/kg, 8.9 x 10(4) colony-forming units-granulocyte/macrophage (CFU-GM)/kg, and 4.5 x 10(6) CD34+ cells/kg. All 14 patients underwent high-dose chemotherapy with PBPC support, the median day to ANC >500 cells/microliter was 10.6, and the median day to platelets >20,000 cells/microliter was 13. The day of 90th percentile platelet recovery was 15. When compared to PBPCs mobilized by cyclophosphamide followed by GM-CSF, the use of PIXY321 may confer an advantage of enhanced platelet recovery.

Blood stem cell transplantation: from preclinical to clinical models.

This introductory statement to the International Symposium "Ten Years of Blood Stem Cell Transplantation in Heidelberg" provides the opportunity to review the experimental work that was necessary to set the stage for the first successful clinical studies to use blood-derived stem cells to treat hemopoietic and other malignancies. The Ulm University research group used the preclinical canine model to systematically and extensively explore the possibilities and limitations of the therapeutic use of blood-derived hemopoietic stem and progenitor cells. It became clear that blood stem cells are physiological elements of the circulating blood, that their concentration can be drastically increased by chemical and biological means, that they do not lose their function during appropriate cryopreservation, and that they can be "purified" and used successfully to restore hemopoiesis after myeloablative conditioning both in the autologous and allogeneic situation. If compared to fetal liver-derived stem cells, there is excellent experimental evidence that fetal liver-derived stem cells may have even more potential in their ability to restore hemopoiesis, and it is evident that much more experimental work is needed.

The additive effect of peripheral blood stem cells, harvested with low-dose cyclophosphamide, to autologous bone marrow reinfusion on hematopoietic reconstitution after ablative chemotherapy in breast cancer patients with localized disease.

The additive effect of peripheral blood stem cells (PBSCs) to autologous bone marrow transplantation (ABMT) on haematopoietic reconstitution, after ablative chemotherapy in patients with locally advanced breast cancer, was evaluated. Patients were treated with induction chemotherapy, followed by ablative chemotherapy consisting of mitoxantrone and thiotepa. Group I (n = 14) received ABMT and granulocyte macrophage-colony stimulating factor (GM-CSF), group II (n = 11) received ABMT, PBSCs and granulocyte-colony stimulating factor (G- CSF). PBSCs were harvested after a low-dose cyclophosphamide (750 mg/m2), followed by G-CSF. Stem cell harvest was routinely started 12 days after cyclophosphamide. Compared to group I, group II showed a significant reduction in the median number of days for leukocytes < 0.5 x 10(9)/L 4.5 days, leukocytes < 1.0 x 10(9) / l 5.5 days, platelets < 20 x 10(9)/ l 9 days and platelets < 40 x 10(9) / l 12.5 days. The median number of transfusions of platelets fell from 11.5 to 7 and of red blood cells from 8.5 to 6. The median hospitalisation duration declined from 40.5 to 30 days, fever above 38 degrees C with 7.5 days, fever above 38.5 degrees C with 4 days and antibiotic treatment with 8.5 days in group I versus group II. Improvement of haematological recovery, duration of fever and hospitalisation was observed by the addition of PBSCs, obtained after a relatively low-dose cyclophosphamide and G-CSF and stem cell pheresis on fixed days, to autologous bone marrow and growth factor in the period after ablative chemotherapy.

[Potential value of hyperbaric oxygenation in the treatment of post-radiation myelopathies]. / Intérêt potentiel de l'oxygénothérapie hyperbare dans le traitement des myélopathies post-radiques.

We describe 9 patients with radiation myelopathy treated by hyperbaric oxygenation (HBO). In this retrospective study, six out of nine (66%) could have been stabilized or improved by HBO. Physiopathological mechanisms of radiation myelopathy remain controversial and incompletely known. We discuss the putative mechanisms of the beneficial action of HBO on radiation myelopathy. Controlled studies are required to clarify the interest of HBO in this disease.

High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy.

Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow-up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.

The role of hematopoietic growth factors in transfusion medicine.

Hematopoietic growth factors have already had an enormous impact on transfusion practice by eliminating or reducing the need for red blood cell transfusions in a variety of anemic states characterized by an absolute or relative decrease in erythropoietin. In addition, GM-CSF and G-CSF have stimulated the production of autologous neutrophils in febrile neutropenic patients in whom granulocyte transfusions had been considered ineffective. With the discovery of c-Mpl ligand and the promising results obtained with IL-11 and IL-3, a combination of growth factors that successfully stimulate platelet production may soon be identified. This first era in the clinical application of hematopoietic growth factors has been characterized largely by treatment of the patient to stimulate production of autologous cells or to enhance the ability of transplanted hematopoietic progenitor cells to repopulate the patient. The use of G-CSF to increase the yield of granulocytes harvested by apheresis procedures and to mobilize peripheral blood stem cells in allogeneic donors has initiated a new era in which the cell donor is treated to enhance cell production and enhance the repopulating ability of hematopoietic progenitor cells. As our understanding of hematopoiesis grows, scientists will be able to identify growth factors to overcome or correct deficient hematopoiesis. Increasingly, component transfusions will be reserved for life-threatening situations in which endogenous cell production cannot be stimulated or cell production will be too slow to prevent life-threatening events.

Haemopoietic growth factor and dose intensity in high-grade and intermediate-grade lymphoma.

Here we review the evidence that cytotoxic dose intensity is an important determinant of outcome in high- and intermediate-grade non-Hodgkin's lymphoma. The results of retrospective analyses and prospective studies support this proposition but confirmatory studies are required. We discuss the role of haemopoietic growth factors and mobilized peripheral blood progenitor cells to increase dose intensity. Studies using these modalities will enable the importance of dose intensity to be tested.

Cytokine enhancement of peripheral blood stem cells.

The use of cytokines to improve peripheral blood stem cell enhancement and recruitment has recently received close attention. Three main cytokines have been, or are still being, investigated in this way in human clinical trials so far: recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), granulocyte CSF (rhG-CSF) and interleukin 3 (IL-3). While cytokines used alone appear undoubtedly capable of a marked peripheral blood stem cell (PBSC) enhancement, their combination with a chemotherapy priming often increases this phenomenon. This is particularly evident with rhIL-3, which is an earlier acting cytokine than rhGM-CSF and rhG-CSF. rhIL-3 priming alone leads to only a minor elevation of circulating progenitor cells, while its combination with chemotherapy and/or a late acting cytokine may allow enhancement and recruitment of large amounts of PBSC. The effect of cytokines on PBSC enhancement may also be at least partially thwarted by various factors. Additionally, their adequate dosage often remains uncertain. So it is presently too early to determine what is actually the most appropriate cytokine or cytokine combination to improve PBSC enhancement. Also the risk of stimulation of tumor clonogenic cells in some malignant diseases remains, and the experimenters should be as cautious as possible to not jeopardize the patients' safety.

Is our current strategy in manipulating hemopoiesis in autologous transplantation correct?

Autologous hemopoietic stem cell rescue following high-dose chemoradiotherapy is increasingly used in the treatment of lymphohemopoietic malignancy and selected solid tumors. While encouraging disease control has been reported in acute leukemia, lymphoma, multiple myeloma and breast carcinoma, such an approach suffers from a number of limitations. This review addresses a number of issues that may lead to better stem cells for transplant: which stem cell rescue provides the most rapid hemopoietic reconstitution, how can we get sufficient high quality stem cells for transplant to ensure complete and sustained reconstitution, what are the predictors of rapid and sustained hemopoietic reconstitution, what impact on hemopoietic reconstitution purging and positive selection technology may have, and how can we abrogate the obligatory delay to blood count recovery.

Is blood or bone marrow better?

Hematopoiesis that has been ablated with high-dose radiation-chemotherapy can be restored with either autologous peripheral stem cell transplantation (PSCT) or autologous bone marrow transplantation (ABMT). Characteristics unique to either type of transplant make one preferable to the other in certain clinical situations. When marrow metastases preclude ABMT, blood provides a suitable source of precursors for autografting. Peripheral cells are more time consuming to collect and more labor intensive to process and store. The peripheral autograft product can be manipulated with mobilization techniques (chemotherapy and/or cytokines) to provide more rapid recovery of granulocytes and perhaps red cells and platelets, while transplantation of manipulated marrow autografts has not yet been reported. Further advances in both ABMT and PSCT will provide additional opportunities to improve the outcome of patients treated with high-dose therapy.