Structures already discussed alongside bone marrow neoplasm in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
RCSB Protein Data Bank · entry 4MXO · 2.105 Å · ligand Bosutinib (DB8). Experimental structure, not a prediction.
Myeloma has an annual incidence of 2–4 per 100,000 in the UK, with a median age at diagnosis of 70 and a median survival for all patients of 3 years; less than 3% survive more than 10 years. Melphalan introduced in 1958 produced clinical responses in 40% of patients, and adding prednisolone improved the response rate by 20% and extended survival by about 5 months. The 5th MRC Myelomatosis Study found ABCM (doxorubicin, carmustine, cyclophosphamide and melphalan) superior to melphalan alone, with a modest increase in median survival from 24 to 32 months. A meta-analysis of 18 trials covering over 3800 patients found no significant difference in 2-year survival between melphalan-prednisolone and combination chemotherapy, though two omitted studies had found a benefit for combination chemotherapy in advanced disease. For patients aged under 65 with no other significant illness, high-dose melphalan with autologous stem-cell rescue produces complete remission in over 30% of patients, and 80% survive more than 3 years, but no survival plateau has been identified. The French IFM90 trial showed improved event-free and overall survival for autologous transplantation over conventional chemotherapy. Allogeneic transplantation is limited to patients under 55, excluding 75% of myeloma patients; the European Bone Marrow Transplant Group reported 162 matched related allografts with 66% achieving complete remission, a 4-year survival rate of 32%, and treatment-related mortality of 40%. Interferon-alpha maintenance reduced relapse rate from 56% to 24% at 33 months in one Italian study, but a recent MRC study found no survival benefit, and a meta-analysis of 24 randomised trials involving 4000 patients showed only a moderate improvement in relapse-free survival and a minor improvement in survival.
For relapsed disease, VAD (high-dose dexamethasone with vincristine and adriamycin) produces remission in about 55% of relapsing patients and 30% of those with primary resistant disease. For VAD-resistant patients, trials of P-glycoprotein-blocking drugs such as verapamil, cyclosporin A and PSC-833 in combination with VAD were underway as of 1999. Clinical responses to anti-IL-6 monoclonal antibodies were substantial but transient. By 2013, the introduction of thalidomide, lenalidomide and bortezomib had markedly improved outcomes, though the review does not give specific survival or response numbers for these agents. A 2006 study of thalidomide-dexamethasone as front-line therapy in 32 newly diagnosed patients found a probability of at least very good partial response of 19%, including 13% in complete or near complete response. Gene expression profiling identified a 10-gene signature that could predict attainment of near complete response, including CCND2 and CFLAR, both down-regulated in responders.
A 2021 study of 157 patients with malignant neoplasms (59.2% non-Hodgkin lymphoma, 19.7% Hodgkin lymphoma, 21.0% solid organ malignancy) found bone marrow infiltration in 31.8%, normal morphology with decreased cellularity in 32.5%, and normal morphology with normal cellularity in 35.7%. Cytopenias were present in 56.1% of patients, but there was no association between cytopenia and bone marrow findings (p = 0.086). A 2017 study of 111 follicular lymphoma patients found that rigorous staging at first diagnosis (including bone marrow aspiration and biopsy plus whole-body imaging) was associated with superior progression-free survival for stage I-II patients. What remains missing are prospective trials that stratify patients by the gene signatures or biochemical markers (β2 microglobulin, IL-6, plasma cell labelling index) that might identify who benefits from which sequence of therapy, and funding for such trials in a disease where 75% of patients are too old for allogeneic transplantation and where relapse remains inevitable for the vast majority.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
QJM · 1999 · 35 citations · open access
Treatment of myeloma
AbstractMyeloma is a malignant disease characterized by the clonal proliferation of plasma cells within the bone marrow. It has an annual incidence of 2–4 per 100 000 population, with 2000–3000 new cases per year in the UK, and accounts for 1% of all malignancies. The majority are over 55, with a median age at diagnosis of 70. Myeloma can manifest itself in a variety of ways—bone marrow failure, susceptibility to infection, hypercalcaemia, bony destruction resulting in pain or pathological fracture, renal failure and amyloidosis. It is an incurable illness, with a median survival for all patients of 3 years. Less than 3% survive more than 10 years and the clinical history is usually one of multiple relapses. Since myeloma is usually a disseminated disease at presentation, chemotherapy is the main treatment modality. Some asymptomatic patients with low tumour mass1 need no treatment; however, those patients with extensive bone disease, bone marrow failure, renal failure or a rapidly rising M-protein need treatment. Chemotherapy is continued only until plateau phase is reached, i.e. clinically and biochemically unchanged for 3 months with a stable paraprotein, as there is no evidence that maintenance chemotherapy prolongs survival in patients with myeloma. There is some suggestion, however, that interferon may prolong relapse-free survival.2 In 1958, melphalan was introduced for this condition, producing clinical responses in 40% of patients.3 It has since been used extensively, alone and in combination. Remissions last a median of 2 years and median survival is improved from under 1 year to between 19 and 39 months. Intermittent treatment is favoured, as it induces remission sooner and increases the response rate with less marrow suppression. This modality is limited by the development of drug resistance, with inevitable relapse. There is also a small risk of the development of a secondary myeloblastic leukaemia or myelodysplasia. Steroids are also effective anti-myeloma agents, reducing bone resorption and lowering M-protein levels. Prednisolone alone is ineffective, although, the addition of prednisolone to oral melphalan improves the response rate by 20% and extends survival by about 5 months.4 The limited success of monotherapy and steroids in myeloma, stimulated the development of combinations of non-cross-reactive agents. Investigators have looked at a variety of alkylating agents, nitrosureas (BCNU or CCNU), vincristine and adriamycin in the regimen, as well as routes of administration, schedules of drug dose and treatment interval. Several trials have compared a variety of combination chemotherapy regimens with melphalan and prednisolone (MP).5,6 Despite a clear advantage in terms of remission induction, no clear benefit for either survival or remission duration has been shown for the newer regimens over single-agent alkylating agent plus steroid. The 5th MRC Myelomatosis Study showed that ABCM (doxorubicin, carmustine, cyclophosphamide and melphalan) was superior to melphalan alone, although there was only a modest increase in median survival from 24 to 32 months.7 In a recent meta-analysis reviewing 18 trials8 comparing treatment with MP to combination chemotherapy, over 3800 patients were assessed, and no significant difference was seen in the 2-year survival of either group of patients. However, two studies were omitted where a benefit was found in favour of combination chemotherapy. The South Western Oncology Group9 and the Cancer and Leukaemia Group B10 have both found that combination chemotherapy in patients with advanced disease produced improved survival and response rates. The consensus seems to be that patients with good prognostic features and an expected survival >2 years have a better outcome with melphalan and prednisolone, whereas those with poor-risk features and an expected survival <2 years may do better with combination alkylating agent chemotherapy. This treatment option is available to patients aged <65 with no other significant co-existing illnesses. Marrow rescue allows significant melphalan dose escalation with a marked reduction in the treatment-associated mortality to <10% compared to high-dose melphalan alone. Peripheral blood stem-cells are increasingly being used as marrow rescue and can allow high-dose therapy in those whose marrow is too heavily contaminated for autologous transplantation. Comparing the two sources of marrow progenitor cells reveals no significant difference in survival or relapse rates. Over 30% of patients autografted will enter complete remission and, although the relapse rate is high, 80% will survive more than 3 years. Autografting appears to be most effective when performed early in the disease but no survival plateau has been identified, suggesting that this procedure is not curative. Some studies are now beginning to show a survival advantage for autografting over conventional chemotherapy. The French IFM90 trial11 comparing these two treatment modalities in previously untreated patients showed that both event-free survival and overall survival were improved by the use of autologous bone-marrow transplantation. The MRC's Myeloma VII trial currently underway is also addressing this issue. Trials of purged autologous marrow, either through positive or negative selection, have shown no reduction in the frequency of relapse. Double autografts have little benefit over single autografts, and are currently associated with considerable toxicity. This is a therapeutic option open to only 4% of patients with myeloma, as it is limited by the availability of an HLA-compatible donor and patient age. The upper age limit for allogeneic bone-marrow transplantation is 55, therefore 75% of patients with myeloma are excluded. Despite this, over 500 allografts have been performed in patients with multiple myeloma since the first carried out in the early 1980s using a syngeneic donor. The European Bone Marrow Transplant Group12 report 162 matched related allografts, 66% of patients engrafting achieved complete remission, with a 4-year survival rate of 32%. Treatment-related mortality was very high at 40%. Factors predictive of survival included only one previous line of treatment, female sex of patient, and presence of CR prior to transplant. Most patients appear to relapse with time, although the survival curve tends to plateau at 5 years post-transplant, suggesting that a proportion may achieve `cure'. There is much interest in the possibility of a graft-versus-myeloma effect following allografting, supported by the demonstration of responses to donor leucocyte infusions in patients who have relapsed after allogeneic transplantation.13 Interferon-alpha (IFN) has primarily been studied as a maintenance treatment aimed at prolonging the plateau phase. An Italian group14 compared IFN maintenance with no treatment, and the relapse rate after 33 months of follow-up was reduced from 56% to 24%. A recent MRC study found no survival benefit of IFN use in the first plateau phase,15 although opinion is divided on this issue, and a recent meta-analysis of 24 randomized trials involving 4000 patients showed that IFN produced a moderate improvement in relapse-free survival and a minor improvement in survival.2 The majority of patients with myeloma will relapse following their initial treatment. Once disease relapse occurs, a second course of first-line treatment should be given, and 50% of patients will respond again. However, 30–50% of patients will not achieve a response on first-line therapy (refractory) or will progress on first-line therapy (relapsing) and should be considered for second-line therapies such as VAD (high-dose dexamethasone and an infusion of vincristine and adriamycin). This is the treatment of choice for relapsing disease, unless used as part of an initial protocol, producing remission in around 55% of patients with relapsing disease and 30% of those with primary resistant disease.16 Poor prognostic factors are serum β2 microglobulin>4 mcg/ml, previous anthracycline therapy, hyperdiploidy or a high plasma-cell labelling index% (a marker of plasma cell turnover). For patients that are VAD-resistant, there are few therapeutic avenues left. VAD resistance is thought to arise from upregulation of the MDR-1 gene, leading to enhanced expression of P-glycoprotein (P-gp). Trials of P-gp-blocking drugs such as verapamil, cyclosporin A and PSC-833 in combination with VAD are underway.17 Other treatment modalities being investigated for these patients include high-dose interferon and cytokine/growth factor manipulation. Clinical responses to anti-IL-6 monoclonal antibodies have been substantial but transient. Inhibition of TNF alpha and IL-1β may slow plasma cell and osteoclast development, and all trans-retinoic acid (ATRA) inhibits myeloma growth by down-regulating IL-6R. Studies are currently underway to evaluate their clinical importance.18 In a disease that affects a predominantly elderly patient group and with a high treatment failure rate, supportive measures are as important as primary therapy. Bone pain requires adequate analgesia, although care should be taken with the use of non-steroidal anti-inflammatory drugs, as they may precipitate renal failure in patients with mild renal impairment. Lytic lesions occurring in critical structural sites need orthopaedic intervention, and isolated painful lesions may require local radiotherapy. Bisphosphonates have been shown to slow the progression of bone disease and reduce the rate of pathological fracture even in those without overt lytic disease.19 Acute renal failure is usually irreversible; therefore, prophylactic allopurinol, adequate hydration, treatment of urinary infection or hypercalcaemia and the avoidance of nephrotoxins such as non-steroidal anti-inflammatory drugs or iv contrast in patients with mild renal impairment should be ensured. Hypercalcaemia needs vigorous treatment with intravenous hydration, frusemide, steroids and bisphosphonates. Infection in these patients should be aggressively treated with broad-spectrum antibiotics, however, prophylactic immunoglobulin therapy is not of benefit. Myeloma-associated anaemia may respond to recombinant erythropoietin (Epo).20 Survival for myeloma has improved from a median of 7 months in the 1950s to about 30 months today. Progress in chemotherapy has contributed a great deal to this improvement, although it may also, in part, reflect the improved treatment of infections, renal failure and hypercalcaemia as well as earlier diagnosis. For over 30 years, the gold standard of treatment has been oral melphalan and prednisolone, producing a clinical response in approximately 60% of patients and a median survival of around 36 months. Relapse is unfortunately inevitable in all but a handful and, for the majority, treatment can only hope to produce significant periods of remission with minimal treatment-related morbidity and mortality.21 Recently, improved results have been seen with the introduction of aggressive chemotherapy and bone-marrow transplantation. Marrow ablative therapies produce remissions in virtually all patients, with complete remissions in approximately 1/3. The best response is seen in those with a lower tumour burden, which will reduce the development of secondary resistance. Current treatment is moving towards an approach using sequential therapy.22 This involves induction chemotherapy with VAD or a similar regimen such as VAMP (vincristine, adriamycin and methylprednisolone), proceeding to high-dose therapy, often with some form of stem-cell rescue. This ensures minimal tumour burden prior to high-dose treatment as well as reducing graft infiltration, improving general performance status and allowing recovery of renal function. Relapse remains a problem, although the use of IFN may reduce this by prolonging the plateau phase. High-dose therapy should be given early, before prolonged use of alkylating agents induces stem-cell dysplasia, before significant complications arise from the myeloma, and before drug resistance is significant. Unfortunately, these treatments come at a price, in terms of increased treatment-related toxicity. There also remains uncertainty as to the extra benefits of high-dose treatment with marrow rescue over high-dose chemotherapy alone. We await the current MRC trial with interest. For a very few, there is the tantalising possibility of cure with allografting.23 For those in complete remission after first-line induction therapy, allogeneic bone-marrow transplantation offers the best hope of survival, but comes at a greatly increased risk of toxicity, and it is uncertain if it is superior to autografting for the majority of patients.24 It may soon be possible to identify those poor prognosis patients in whom an allogeneic transplant should be offered at an early stage. Candidate biochemical markers include serum β2 microglobulin, neopterin, IL-6, plasma cell labelling index, CRP or LDH and prognostic clinical features include IgD myeloma or stage III disease at presentation. Many patients will have primary refractory or relapsing disease in whom survival is short despite all current therapeutic modalities. They should therefore be considered for trials of newer agents, drug combinations and therapeutic interventions such as cytokine manipulation or gene therapy. The lack of effective, curative treatment options for patients with myeloma places great importance on effective palliation. While improving survival duration remains elusive in this condition, all possible efforts must be made to ensure quality of life is maximized.
https://doi.org/10.1093/qjmed/92.1.11Clinical Medicine Insights Oncology · 2013 · 24 citations · open access
Current and Emerging Treatment Options for Patients with Relapsed Myeloma
AbstractMultiple myeloma (MM) is a neoplastic disorder. It results from proliferation of clonal plasma cells in bone marrow with production of monoclonal proteins, which are detectable in serum or urine. MM is clinically characterized by destructive bone lesions, anemia, hypercalcemia and renal insufficiency. Its prognosis is severe, with a median survival after diagnosis of approximately 3 years due to frequent relapses. Treatments for patients with relapsed/refractory MM include hematopoietic cell transplantation, a rechallenge using a previous chemotherapy regimen or a trial of a new regimen. The introduction of new drugs such as thalidomide, lenalidomide and bortezomib has markedly improved MM outcomes. When relapse occurs, the clinician's challenge is to select the optimal treatment for each patient while balancing efficacy and toxicity. Patients with indolent relapse can be first treated with a 2-drug or a 3-drug combination. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Autologous stem cell transplantation should be considered as salvage therapy at first relapse for patients who have cryopreserved stem cells early in the disease course. The aim of this review is to provide an overview on the pharmacological and molecular action of treatments used for patients with relapsed/refractory multiple myeloma.
https://doi.org/10.4137/cmo.s8014The Journal of Pediatric Pharmacology and Therapeutics · 2020 · 5 citations · open access
Pharmacokinetics, Efficacy and Safety of Bosutinib in a Pediatric Patient With Chronic Myeloid Leukemia
AbstractBosutinib is a second-generation tyrosine kinase inhibitor indicated for treatment of chronic myeloid leukemia (CML) in adult patients. The safety and efficacy of bosutinib in patients younger than 18 years of age have not been established. We here report the case of a 4-year-old male with CML who was treated with bosutinib during coordination of human leukocyte antigen–matched unrelated bone-marrow transplantation because of insufficient responses to imatinib and dasatinib. The patient achieved a complete cytogenetic response immediately after starting bosutinib at 180 mg/day (290 mg/m 2 /day). Because toxicity was tolerable, the dose was increased to 200 mg/day (330 mg/m 2 /day). A complete cytogenetic response was maintained, but a major molecular response was not achieved 6 months after initiation of treatment with bosutinib. At steady state, maximum plasma concentration, minimum plasma concentration, and area under the plasma concentration-time curve were 89.2 ng/mL, 16.7 ng/mL, and 1017.4 ng·hr/mL, respectively, at 290 mg/m 2 /day; and 141.1 ng/mL, 18.9 ng/mL, and 1278.5 ng·hr/mL, respectively, at 330 mg/m 2 /day. To the best of our knowledge, this is the first case report to show the pharmacokinetics of bosutinib with efficacy and safety in a pediatric patient with CML. This rare case in a very young child with CML can also be valuable reference for clinical practice.
https://doi.org/10.5863/1551-6776-25.8.742Blood · 2006 · 4 citations
Gene Expression Profiling (GEP) of Myeloma (MM) Cells To Predict Attainment (near) Complete Response to Primary Therapy with Thalidomide-Dexamethasone (Thali-Dex) for Newly Diagnosed MM.
AbstractAbstract In recent years, treatment paradigm of targeting the “soil” bone marrow (BM) microenvironment as a means of interfering with the growth of the MM “seed” has provided the rationale for investigational clinical trials of novel agents combined with old drugs in an attempt to maximize tumour response. Thalidomide, which represents an effective treatment strategy for relapsed/refractory MM, actually represents a standard of care also for newly diagnosed MM patients. We have recently demonstrated that thali-dex combination as front-line therapy in preparation for autologous transplantation is superior to VAD in terms of increased rate of response (≥ partial response: 76%) and magnitude of tumour reduction. In particular, the probability to attain at least a very good partial response (VGPR) was 19%, including 13% of patients in complete response (CR) or near CR (nCR). In the present study we adopted a GEP strategy in an attempt to identify a signature able to predict the probability to attain ≥ nCR to combined thali-dex as upfront therapy for patients with newly diagnosed MM. CD138+ samples obtained at diagnosis from 32 patients enrolled in the “Bologna 2002” clinical trial were used throughout the study; all patients were evaluable for response to thali-dex in preparation for autologous transplantation. GEP was performed using the Affymetrix HG133 Plus microarray platform. The Affymetrix output (CEL files) was imported into Genespring 7.3 (Agilent technologies) microarray analysis software, where data files were normalized across chips using GCRMA and to the 50th percentile, followed by per gene normalization to median. Genes differently expressed in subgroups of patients were selected by an ANOVA analysis. Criteria of response were those established by Bladè et al, with the addition of a VGPR and nCR categories. Overall, six of the 32 patients (19%) obtained at least a nCR to thali-dex, whereas the remaining 26 patients either achieved a partial response or did not respond. We identified a gene signature of 162 genes, able to significantly distinguish patients with ≥ nCR from the others (p=0.05). We then adopted a Nearest-Neighbours (NN) classifier (using 3 first neighbours), with a “Leave-one-out Cross Validation” procedure, to identify a list of ten genes able to predict the ≥ nCR in our series of patients (see table). Of interest, the gene list encompasses CCND2, one of the most important cell cycle regulator known to be involved in tumour progression in MM patients and the anti-apoptotic gene CFLAR, both down-regulated in nCR patients. These results could be the first step to adopt microfluidic cards, in an attempt to select at diagnosis patients who will respond very favourably to a particular treatment strategy. Supported by Università di Bologna, Progetti di Ricerca ex-60% (M.C.); Ministero dell’Università e Ricerca Scientifica (MIUR), progetto FIRB, RBAU012E9A_001 (M.C.); and Fondazione Carisbo. gene ID gene name chromosomal location 225792_at HOOK1 1p32.1 236223_s_at unknown 1q22 225282_at SMAP1L 1p35.3-p34.1 239629_at CFLAR 2q33-q34 227027_at GFPT1 2p13 226886_at GFPT1 2p13 205848_at GAS2 11p14.3-p15.2 200951_s_at CCND2 12p13 200628_s_at TSPAN4 14q32.31 242121_at unknown unknown
https://doi.org/10.1182/blood.v108.11.245.245PubMed · 2017 · 1 citations
[Effect of Rigorous Staging at the First Diagnosis on Prognosis of Patients with Follicular Lymphoma].
AbstractBACKGROUND: A survey of early stage follicular lymphoma(FL) revealed that the rigorously staged FL patients at first diagnosis had a better outcome as compared with non-rigorous staged FL patients, but there were no similar reports in China. OBJECTIVE: To explore the relationship between the rigorous staging at first diagnosis and the prognosis of FL patients at different stages. METHODS: The clinical data of 111 patients with newly diagnosed FL from 2008 to 2014 year were collected and analyzed. The rigorous staging included: (1) bone marrow aspiration and biopsy, (2) imaging examination of whole body including CT and ultrasounic scan, or PET/CT, either or both is defined as rigorous staging, or else as non-rigorous staging. RESULTS: The FL patients at I-II stages by rigorous staging showed a superior progression-free survival(PFS) compared with non-rigorous staging patients(P=0.048). For all the patients, the age, serum LDH, bone marrow lesion and more than 3 foci of diameter larger than 3 cm correlated with prognosis in univariate analysis, and multivariate analysis revealed that the age, serum LDH and bone marrow imolvement were the independent prognostic factors. CONCLUSION: Rigorous staging leads to better outcomes, suggesting that accurate and appropriate testing is important for the patients at the first treatment. The close correlation of bone marrow with prognosis indicates that the evaluation of bone marrow is very important for the daily clinical practice.
https://doi.org/10.7534/j.issn.1009-2137.2017.01.022JNCI Journal of the National Cancer Institute · 1995 · 0 citations
BOOK REVIEW
AbstractJournal Article BOOK REVIEW Get access Bone Marrow Disorders: the Biological Basis of Treatment, 2nd ed . A. J. Barrett M. Y. Gordon . Oxford, England : Blackwell Scientific Publications , 1993 , 416 pp., illus. $135.00, ISBN 0-632-03353-3 . STEVEN GORE, M.D. STEVEN GORE, M.D. The Johns Hopkins Hospital Oncology 2-109 600 N. Wolfe St.Baltimore, MD 21287 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 1, 4 January 1995, Pages 54–55, https://doi.org/10.1093/jnci/87.1.54 Published: 04 January 1995
https://doi.org/10.1093/jnci/87.1.54Journal of College of Physicians And Surgeons Pakistan · 2021 · 0 citations · open access
Are Peripheral Blood Counts Predictor of Bone Marrow Infiltration and Hypocellularity in Malignant Neoplasms?
AbstractOBJECTIVE: To determine the association of peripheral blood counts (cytopenia and normal counts) with bone marrow findings in patients with malignant neoplasms. STUDY DESIGN: Descriptive study. Place and Duration of the Study: King Edward Medical University from 2017 to 2019. METHODOLOGY: Patients having malignant diseases, of both gender and all ages, were included. Clinical data and results of bilateral bone marrow aspiration and biopsy were noted. Results were categorised as groups with bone marrow infiltration, normal morphology with normal cellularity and normal morphology with decreased cellularity. Results were analysed using SPSS V21 applying Chi-square test, keeping the confidence interval 95% and p-value of <0.05 as significant. RESULTS: A total of 157 patients were included (107 men, 50 women). The main categories of neoplasm included non-Hodgkin's lymphoma [93 (59.2%)] Hodgkin's lymphoma [31 (19.7%)], and solid organ malignancy [33 (21.0%]. Bone marrow infiltration was seen in 50 (31.8%) patients, normal morphology with decreased cellularity in 51 (32.5%) and normal morphology with normal cellularity in 56 (35.7%) patients. Cytopenias were seen in 88 (56.1%) patients (out of these 28 (31.8%) had bone marrow infiltrarion, 32 (36.4%) had decreased cellularity and 28 (31.8%) with normal cellularity). In 69 (43.9%) patients with normal CBC, 22 (31.9%) had infiltration, 19 (27.5%) had decreased cellularity and 28 (40.6%) had normal cellularity. No association of cytopenia with bone marrow results was obtained (p = 0.086). CONCLUSION: Bone marrow infiltration and hypocellularity are not reflected by peripheral blood counts. Therefore, bone marrow biopsy remains decisive in patients with malignant neoplasm for disease staging and selection of treatment options. Key Words: Peripheral blood counts, Bone marrow infiltration, malignant neoplasms, bone marrow hypocellularity.
https://doi.org/10.29271/jcpsp.2021.01.79Blood · 2014 · 0 citations
Decrease in Transfusion Needs in Patients with Higher-Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia Treated with 5-Azacytidine. a Retrospective Study
AbstractAbstract Introduction The hypomethylating agent 5-azacytidine (AZA) has been the standard of care for higher risk Myelodysplastic Syndromes (MDS) for the last few years. Its efficacy has been proven in large clinical trials, and its safety has been shown to be superior to that of conventional treatments. We have conducted a retrospective study about the efficacy and safety of 5-azacytidine, as reported and analyzed in our center. Patients and Methods Forty four consecutive patients with MDS or Acute Myeloid Leukemia (AML) with 20-30% bone marrow blasts that were treated with AZA during the last 63 months were included in the study. The clinical and laboratory characteristics of the patients were recorded, and the efficacy and safety data were analyzed. Results The epidemiologic and hematologic characteristics of the patients are shown in Table 1. The median overall survival was 13 months (1-101) and there was no primary treatment failure (Table 2). Serious adverse events consisted mostly of neutropenic infections (blood stream and pneumonia) (Table 3). Discussion Treatment with AZA offered a favorable (complete and partial) response in 34.1% of the patients, and an overall survival of 13 months, with generally predictable toxicities, although hospitalization was frequently inevitable during the first treatment cycles, when supportive treatment was a significant part of the management. A valuable observation is that there was a considerable decrease in the patients’ transfusion needs following treatment (p<0.0001). Our results are consistent with the results of other clinical trials and point out the need for investigational 5-azacytidine combinations. Table 1. Epidemiologic and hematologic characteristics. Male: Female ratio 30:14 (2.1 : 1) Age, Median (Range) 73 (54-81) WHO classification of MDS/AML, N (%) RAEB-I RAEB-II RCMD-RS RCMD RARS CMML AML 9 (20.5) 18 (40.9) 2 (4.5) 3 (6.7) 1 (2.3) 4 (9.1) 7 (15.9) IPSS classification, N (%) Low Intermediate-1 Intermediate-2 High Not Applicable (AML) 0 (0) 3 (6.8) 29 (65.9) 5 (11.4) 7 (15.9) Complete Blood Count Parameters, Median (Range) Hemoglobin (g/dL) Absolute Neutrophil Count (x109/L) Platelet count (x109/L) 8.55 (4.5 - 12.5) 1.08 (0.0 – 16.3) 80.0 (2 – 820) Transfusion dependence, N (%) 39 (88.6) Transfusions per month, Median (Range) 3 (0 – 7) Table 2. Efficacy data AZA cycles, Median (Range) 5 (1-22) Actual AZA dose (mg/m2/cycle), Median (Range) 75 (59-75) Actual cycle duration (days), Median (Range) 28 (28-40) Dose reductions due to sustained neutropenia, N (%) 6 (13.6) Temporary AZA interruption, N (%) 26 (59.1) Reason Sustained cytopenia 10/26 (38.5) Neutropenic Infection 15/26 (57.7) Hemorrhagic Complication 1/26 (3.8) Permanent AZA discontinuation, N (%) 23/44 (52.3) Reason AML transformation 17/23 (73.9) Recurrent or severe infection 4/23 (17.4) Pyoderma gangrenosum 1/23 (4.3) Allogeneic Bone Marrow Transplantation 1/23 (4.3) AZA cycles till response (according to the IWG criteria), Median (Range) 4 (1 – 7) Response (IWG criteria), N (%) Complete response Partial response Stable disease Failure 7 (15.9) 8 (18.2) 29 (65.9) 0 (0) Overall survival (months), Median (Range) 13 (1 – 101) Post treatment transfusion dependence, N (%) 34 (77.3) Transfusions per month (post-treatment), Median (Range) 1 (0 – 5) Death rate, N (%) 29/44 (65.9) Cause of death, N (%) Infection Hemorrhage Cardiac dysrhythmia 24/29 (82.8) 3/29 (10.3) 2/29 (6.9) Table 3. Safety data Clinical adverse events, N (%) 29/44 (65.9) Neutropenic Infections 26/29 (89.7) Bloodstream Infection 9/26 (34.6) Lower respiratory infection 10/26 (38.5) Neutropenic Fever 8/26 (30.1) Septic shock 2/26 (7.7) Hemorrhagic events 2/29 (6.7) Cerebral hemorrhage (Grade 5) 1/2 (50.0) Epistaxis (Grade 3) 1/2 (50.0) Other (pyoderma gangrenosum) 1/29 (3.4) Laboratory incidents1, N (%) 44/44 (100) All grades Grades 3/4 Neutropenia 36/44 (81.8) 34/44 (77.3) Anemia 44/44 (100) 24/44 (54.5) Thrombocytopenia 31/44 (70.5) 21/44 (47.7) Supportive treatment (during AZA administration), N (%) GCSF administration 16/44 (36.4) Erythropoietin administration 7/44 (15.9) Red blood cell transfusions 39/44 (88.6) Red blood cell transfusions (units/cycle), Median (range) 3 (0-7) Pooled random donor platelet transfusions 17 (38.6) 1According to the CTCAE Version 4.0 Disclosures No relevant conflicts of interest to declare.
https://doi.org/10.1182/blood.v124.21.5608.5608Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
