In Western countries, slow gonorrhea accounts for one-third of all leukemias. Despite its high prevalence in European and North American countries, treatment options for slow gonorrhea were very limited until the early 1890s. Thereafter, treatment options were continually broadened from simple conservative treatment with alkylating agents to modern immunotherapies such as nucleoside analogues and monoclonal antibodies. The emergence of new options has prompted the clinic to face a choice of treatment options. Therefore, it is important to consider the patient’s age, body, general condition, and risk of disease progression or recurrence.
I. Indications for treatment
Patients with chronic gonorrhea are highly heterogeneous; some patients with “quiescent” chronic gonorrhea have no clinical manifestations for many years, while others are already in the progressive stage in the early stages. In conclusion, treatment or not is based on the recommendations of international treatment guidelines.
Treatment is mainly aimed at patients in the progressive stage and those with combined bone marrow failure (Rai stage III or IV, Binet stage C), since the overall survival of these patients is only 1-2 years with only supportive therapy. Conversely, according to the analysis of available data, active treatment for patients in the early stages (Rai stage 0-II, Binet stage A or B) does not prolong the survival of patients. Therefore, in addition to clinical trials, treatment for patients in the non-progressive stage should only be administered if the patient has one of the following symptoms: severe group B symptoms (weight loss of 10% or more within six months, fever greater than 38°C, night sweats); extreme fatigue due to exclusion of other diseases; symptoms of compression due to severe liver, spleen or lymph node enlargement; lymph node doubling time of less than six months; or combined autoimmune anemia or thrombocytopenia without response to glucocorticoids.
Recently, the choice of traditional treatment strategies has been challenged by the emergence of new prognostic indicators, including: chromosomal abnormalities such as 11q- or 17 q-, positive IgH gene rearrangements, overexpression of ZAP70 or CD38, and high levels of thymidine kinase and β2-microglobulin (β2-MG) in the serum are all factors of poor disease prognosis. It has been postulated that in non-progressive asymptomatic CLL with these unfavorable factors can benefit from early first-line therapy. This study is currently being done in relevant clinical trials, but the final results are not yet known. Therefore, except for clinical trials, treatment is still not recommended for patients who do not have clinical signs of disease progression but only have the above adverse indicators.
Choice of first-line treatment
Treatment options for chronic gonorrhea include single-agent chemotherapy and multi-drug combination chemotherapy. To date, no treatment has been able to cure the disease or to improve overall survival. However, with modern treatment regimens, remission rates of 95% can be achieved, with sustained remission for 4-5 years. The efficacy and toxicity of different treatment options vary widely, so the choice of treatment option should be individualized. The treatment options are described below.
(i) Glucocorticoids
For patients with combined autoimmune hemolytic anemia or immune thrombocytopenia, prednisone is an effective drug. The common method is 40-60mg/d, gradually reducing the dosage after one week, and stopping the drug after one week of reduction. After that, it continues to be maintained at 60mg/d for 5 days per month. However, monotherapy is slow gonorrhea, with a low rate of complete remission and easily combined with complications such as infection, water and sodium retention, and secondary hyperglycemia.
(II) Alkylating agent-based chemotherapy
1.Phenylbutyric acid nitrogen mustard
Prior to the late 1880s, nitrogen mustard phenylbutyrate was widely used, either alone or in combination with prednisone. It is well tolerated orally and has few adverse effects. The common dose of continuous dosing is 2-4 mg/d, which can be gradually increased to 6-8 mg/d if tolerated, maintained after efficacy and gradually reduced; intermittent therapy can also be used, with a total dose of 0.4-0.7 mg/kg given every 2-4 weeks for 1-4 days, with similar efficacy in both dosing methods and minimal bone marrow toxicity in the latter. Phenylbutyrate monotherapy has an overall response rate of 37%-72%, but complete remission rates are only 0%-7%, with relapse often occurring earlier than in patients treated with nucleoside analogs.
Although benzodiazepine is no longer an option for young and fit patients, the results of currently available clinical trials suggest that benzodiazepine remains the first choice for older and less fit patients. Although complete remission is not achieved in patients over 65 years of age with chronic gonorrhea, the disease-free progression and overall survival rates are similar to those with nucleoside analogs.
2. bendamustine (B)
Bendamustine is a nucleoside analogue hybridized with alkylating agent. The US FDA approved Cephalon’s bendamustine hydrochloride for slow gonorrhea on March 21, 2008. Its dose is 50-60 mg/m2/d for 3-5 days, repeated once every 4 weeks or 100-120 mg/m2 every 3-4 weeks
The latest phase III clinical trials suggest that bendamustine is a safe and highly effective treatment for lymphatic gonorrhea. The complete remission rate induced by bendamustine alone was in 30%, the overall remission rate was in 68%, and the progression-free period was significantly longer than that in the benzodiazepine group (22 vs. 9 months). However, it remains to be clarified whether bendamustine is superior to benzodiazepine in elderly and poorly fit patients at first diagnosis.
3.Anthracycline-based chemotherapy
The overall response rate of CHOP or CAP regimen is 58%-72%. However, these two regimens have no significant advantages over the nucleoside analog fludarabine alone in terms of induction of remission, duration of remission, overall survival and toxicity in patients with primary chronic gonorrhea. They are not currently preferred for untreated primary cases.
(C) Nucleoside analogue-based chemotherapy
1.Fludarabine
The emergence of fludarabine (F), a late stage nucleoside analogue, in the 1880s ushered in a new era of first-line treatment for chronic gonorrhea. Fludarabine was administered at a conventional dose of 25 mg/m2/d in 30-minute drips for 5 days, repeated over 4 weeks. The results of three phase III clinical trials showed complete remission rates of 20%-40% and overall remission rates of 63%-71% in patients with primary chronic gonorrhea treated with fludarabine. Median progression-free survival exceeded 25 months compared to nitrogen mustard phenylbutyrate, but there was no improvement in overall survival. In a current clinical trial in older patients >65 years of age, fludarabine had no advantage over benzodiazepine in extending progression-free survival (18-19 months in both groups). There was little difference in toxicity between the two, except that fludarabine had a more significant suppression of the bone marrow. For patients who relapsed, patients in the benzodiazepine group were more often treated with salvage therapy than those in the fludarabine-treated group (26% versus 12%) and responded better. These findings and a recent meta-statistical analysis suggest that the past benefits of fludarabine monotherapy for slow onset gonorrhea may have been overestimated.
Clinical trials have shown that fludarabine in combination with cyclophosphamide (FC) is more effective than F alone, while FC is more toxic than F alone. fludarabine 20-30 mg/m2/d for 3 days and cyclophosphamide 200-300 mg/m2/d for 3 days in a 28-day course. The phase III clinical trial suggested that the FC regimen was effective in improving the complete response rate (22%-39% vs. 6%-15%) and overall response rate (70%-95% vs. 50%-83%) and significantly prolonged progression-free survival (41-48 months vs. 18-20 months), however, overall survival was not significantly improved.
Based on reasonable phase III clinical trials, the FC regimen is currently used as the standard first-line treatment regimen for slow gonorrhea. The disease-free survival is currently seen to be better than that of single-agent chemotherapy regimens with alkylating agents and nucleoside analogs. The lack of significant improvement in overall survival is most likely not due to the poor efficacy of FC. Recent study data suggest that it is likely that patients receiving FC regimens as first-line therapy have limited second-line treatment options and are similarly less likely to benefit from second-line regimens. It is important to note that the advantage of FC in terms of response rates and sustained remission rates is primarily in younger patients. In patients older than 70 years of age although FC has a good response rate, treatment is often interrupted due to the high incidence of life-threatening complications. Therefore, usually FC combined with chemotherapy is used in patients in good physical condition. The drug dose should be adjusted for patients in poor general condition or elderly patients.
2.Cladribine (2′-chlorodeoxyadenosine)
It is another adenosine analogue, the common dose is 0.12mg/kg/d, continuous drip for more than 2 hours, for 5 days, one course of treatment in January. In patients treated with alkylating agents, the efficiency of treatment with this drug is 40-60%. However, treatment with this drug does not prolong survival, with a median time to partial remission of about 9 months. There are currently clinical trials where cladribine is used in combination with cyclophosphamide for comparison with the FC group. The main treatment-related side effects are thrombocytopenia, bone marrow suppression and a long-term decrease in blood T-cell levels. Fungal and viral infections are common causes of treatment failure.
3. Pentostatin (2′-deoxycoformycin, P)
It is a purine analogue synthesized from streptomycin antibiotic, which can inhibit adenosine deaminase. The applied dose of 4 mg/m2 is administered intravenously once a week, and after 3-6 weeks of treatment, the dose is changed to once a month for a 6-month treatment cycle, with a complete or partial remission rate of 25%.
(iv) Immunotherapy and chemotherapy containing antibodies
1.Rituximab (anti-CD20 monoclonal antibody)
Rituximab binds to CD20 on the surface of CLL cells, thereby killing CLL cells. Because of the low expression of CD20 on the surface of CLL cells and the presence of soluble CD20 molecules in plasma, rituximab is cleared too quickly in CLL patients and requires a higher dose to be effective. Two clinical trials have been conducted using F or FC in combination with rituximab for the treatment of LHC (FR or FCR), with an efficiency rate of 90-95% and a complete remission rate of 50-70%. The German Working Group on Lymphoma is currently conducting a clinical trial of FCR versus FC randomized controlled therapy for lymphoma (GCLLSG), with enrollment completed in 2006. In January 2008, the data management informed the sponsors that FCR was superior to FC according to the available reliable data, but the final analysis of the results is still in progress. This may mean that FCR will be the first-line treatment option for patients in good health in the near future. Therefore, it is necessary to continue the regimen for patients in good health, but for patients in poor general condition and older patients, it is not a first-line treatment option, considering patient and tolerability and drug toxicities.
In addition to the FCR regimen, pentostatin in combination with cyclophosphamide and bendamustine have been used in combination with rituximab for the treatment of CLL (PCR or BR). In comparison with FR and FCR, it is noteworthy that the PCR regimen has a better anti-leukemic effect in elderly patients, along with relatively mild toxicity. Future clinical trials will focus on optimizing FCR regimens or applying immunotherapy regimens, such as FR, PCR and BR, which may have the same efficacy but less toxicity than FCR.
2.Alemtuzumab (anti-CD52 monoclonal antibody)
Alemtuzumab is a CD52 protein that binds to the surface of CLL cells to induce apoptosis. Compared with rituximab, alemtuzumab alone can have a significant anti-leukemic effect. It is administered as 30 mg intravenously three times a week for 12 weeks, and 30 mg subcutaneously three times a week for at least 6 weeks to reduce side effects such as fever and rash due to intravenous application. Data from a recent phase III clinical trial showed that the use of alemtuzumab for the treatment of primary chronic gonorrhea was effective in improving response rates (83% overall response rate, 24% complete response rate), progression-free survival, and cycle time to change treatment regimens (23 months) compared to traditional alkylating agents.
In particular, the use of alemtuzumab is particularly important in patients with P53 mutations or deletions in slow-growing gonorrhea, as this group of patients is often ineffective to chemotherapy alone and in combination with chemotherapy (including FCR). To date, alemtuzumab is the only drug capable of overcoming P53 gene-mediated resistance to chemotherapeutic agents, and although there is insufficient basis to recommend alemtuzumab for patients with P53 deletion or mutation, enrollment in relevant clinical trials is still recommended for such patients.
Alemtuzumab has also been used for consolidation therapy after first-line therapy, such as in patients treated with F or FC. Progression-free survival has been shown to be longer in patients treated with consolidation therapy with alemtuzumab than in those treated with observation alone. However, the persistent T-cell suppression after treatment, which leads to the emergence of life-threatening severe infections, makes these advantages less obvious. Future directions will be to further explore the role of alemtuzumab and the options for consolidation therapy.
III. Indications for salvage therapy
Salvage therapy is generally indicated when patients present with the following clinical signs of disease progression: severe group B symptoms (weight loss of 10% or more within six months, fever >38°C, night sweats); extreme fatigue excluding other diseases; signs of compression due to severe hepatomegaly, splenomegaly or lymph node enlargement; lymph node multiplication of less than 6 months; or combined autoimmune anemia or thrombocytopenia that No response to glucocorticoids.
Microresidual lesions (MRD), which can be monitored by flow cytometry or PCR, can be suggestive of disease progression before clinical manifestations appear, and therefore monitoring MRD for early detection of disease progression is currently advocated, but is still in the experimental phase and requires further randomized clinical trials. Outside of clinical trials, however, the indications for salvage therapy are still based on the above-mentioned indicators.
IV. Selection of salvage treatment options
The salvage treatment options for relapsed CLL are not yet standardized. For patients with advanced relapse (patients with traditional single-agent chemotherapy valid for more than one year or modern immunochemotherapy regimens effective for more than 2 years) first-line treatment regimens can be used.
For patients in short remission, a change in treatment regimen is required. For patients who have been previously treated with nucleoside analogs or immunochemotherapy, treatment with bendamustine alone has little success. Bendamustine alone or in combination with other agents is effective in some patients with relapsed or refractory CLL. The anthracycline epi-amycin and the combination with fludarabine (EF regimen) are more effective in relapsed CLL, but are not superior compared to FC combination chemotherapy. Drugs that inhibit cell growth (fludarabine, fludarabine combined with cyclophosphamide, pentostatin, bendamustine) have been used in combination with rituximab or alemtuzumab (FA, CFAR, FCR, PCR, BR) to treat patients with relapsed CLL. Autologous or allogeneic hematopoietic stem cell transplantation is also used in patients with relapsed or refractory CLL.
V. Autologous transplantation
Statistics of 72 patients in five Finnish centers during the decade 1995-2005 showed a mean age of 57 (38-69 years), a mean time from transplantation to diagnosis of 32 months (6-181 months), and a mean use of one treatment prior to transplantation. The most used pretreatment regimen was TBI + cyclophosphamide (38 of 53%), there were no early treatment-related deaths, and disease recurrence or progression occurred in 37% of patients at about 28 months of follow-up. Progression-free survival and overall survival were 48 months and 95 months, respectively.
A study from the Medical Research Consortium (MRC) enrolled patients with primary chronic gonorrhea, 65 of 115 patients underwent autologous stem cell transplantation after fludarabine treatment, and only one patient died from early complications of transplantation, with a 74% complete remission rate (48/65), 77.5% overall 5-year survival, and 51.5% 5-year progression-free survival after transplantation. Data from 20 of these patients who were able to be analyzed were analyzed, and 16 achieved complete molecular biological remission within 6 months of transplantation. Of note, in 5/65 (8%) patients developed acute myeloid leukemia or MDS secondary to transplantation.
Although the mortality associated with early transplantation is low, patients with CLL are prone to co-infection relative to other diseases. Whether this is due to immunodeficiency associated with CLL itself or secondary to post-transplant immunosuppression is not known. The timing of autologous stem cell collection needs to be further investigated, but the cells should be collected at least 3 months apart from fludarabine.
Relapse after autologous transplantation remains a major problem at this time, and flow cytometry and PCR are currently being used to monitor disease relapse. Molecular remission can be achieved in two-thirds of patients, but not permanently, so molecular monitoring allows early detection of disease progression.
Theoretically, tumor cells within the graft may increase the risk of disease recurrence. Many research centers are looking to improve outcomes through graft decontamination. One approach uses monoclonal antibodies to B cells to remove tumor cells, and another uses CD34 monoclonal antibodies to screen stem cells. However, both are ineffective and lead to stem cell loss, which can be achieved by adding alemtuzumab or melphalan monoclonal antibody to the pretreatment regimen for in vivo decontamination. A clinical trial using high-dose alemtuzumab is currently underway in the German Chronic Gonorrhea Study Group. In this study, 16 patients were treated with alemtuzumab at an average dose of 103 mg. Initial skin engorgement was observed and required further analysis. 12 patients (87%) developed skin engorgement between 43 and 601 days after autograft, 7 of which were consistent with a GVHD diagnosis, which did not occur in the TBI/cyclophosphamide group.
Autograft GVHD is an autoimmune reaction mediated by the recognition of self-histocompatibility type II antigens by self-effector T cells and is usually self-limiting. All patients require immunosuppressive therapy and the average cycle is 517 days, a trial that was interrupted by high mortality due to non-recurrent complications such as infection. The use of alemtuzumab in combination with other immunosuppressive agents was effective in preventing GVHD in allogeneic transplants, and therefore it was postulated that excessive immunosuppressive regimens, clearing regulatory CD4 and CD8 T cells and natural killer cells, would lead to the development of autoimmune disease. In patients pretreated with alemtuzumab/TBI/cyclophosphamide there is a severe CD8 lymphocytopenia at one year post-transplant. It is therefore recommended that patients undergoing in vivo decontamination with alemtuzumab in subsequent therapy should be treated with a less immunosuppressive pretreatment regimen such as BEAM and avoid TBI as much as possible.
In 34 patients who responded to fludarabine treatment with standard doses of alemtuzumab (10 mg subcutaneously three times a week for six weeks), the complete remission rate increased from 35% to 79.5%, and residual lesion clearance was achieved in 56%. 92% of patients underwent successful stem cell harvesting. 18 patients underwent autologous transplantation, and 17 were in Complete remission status.
VI. Clear allogeneic hematopoietic stem cell transplantation
In contrast to autologous transplantation, allogeneic transplantation also has a graft-versus-leukemia effect. This contributes to better disease control and even cure, but is accompanied by increased cost and toxicity. Deaths from allogeneic transplantation are often associated with pretreatment regimens and acute and chronic GVHD. There is also a significant increase in the occurrence of infections due to GVHD and immunosuppressive drugs.
The feasibility of allogeneic hematopoietic stem cell transplantation for the treatment of slow gonorrhea was first described in 1988 with eight patients treated, five surviving and in complete remission 27 months after transplantation, with treatment-related mortality in the range of 46-50%. Of the 25 allogeneic transplanted CLL patients performed at the Fred Hutchinson Cancer Center, 14 developed acute GVHD of grades II-IV and 10 developed extensive chronic GVHD. 100 days of non-native disease relapse resulted in treatment-related mortality rates as high as 57% in the Maryland, cyclophosphamide pretreatment group and 17% in the TBI pretreatment group. 5-year survival was 32% in the 25 patients . All patients pretreated with Marilan, cyclophosphamide died within 3 years. The overall 5-year survival rate was 56% in the 14 patients who used TBI alone as a pretreatment regimen, suggesting the possibility of long-term survival in this group.
There are no data to support an increase in efficacy by increasing the dose. In fact, the use of allogeneic transplantation mainly exploits its GVL effect, avoiding disease recurrence through acute or chronic GVL effects. This can be achieved by donor lymphocyte infusion after transplantation or after discontinuation of immunosuppressive drugs. The amount and timing of lymphocyte infusion is being explored.
Unrelated donor transplantation is currently being attempted because the chance of a full sibling donor match is only 1 in 4. Of the 38 patients who underwent unrelated donor transplantation, the 5-year overall survival rate was 33%, the treatment-related mortality rate was 38%, and the disease progression rate was 32%. Notably, 45% developed 2nd-4th degree acute GVHD and 85% had chronic GVHD. therefore, it is believed that although long-term survival can be achieved with unrelated donor transplantation, treatment-related mortality is very high and therefore unrelated donor transplantation with incomplete compatibility is not recommended.
(I) Autologous transplantation versus allogeneic transplantation
The most recent M.D. Anderson Cancer Center data show that for 14 cases that were relapsed or refractory after fludarabine treatment, 13 (87%) achieved complete remission after allogeneic transplantation. At the time of reporting, nine patients (53%) were alive and in complete remission with a mean follow-up period of 36 months. In a phase II study conducted at the Dana Farber Cancer Institute, which included 162 high-risk patients with acute gonorrhea seen from 1989 to 1999, 25 underwent sibling allogeneic allogeneic transplantation with de-T and 137 underwent autologous stem cell transplantation with B-cell purification because of the absence of a sibling donor, the mortality rate within 100 days was 4% in both groups, with a mean follow-up of 6.5 years, with no difference in There was no difference in overall survival (autologous 58% allogeneic 55%). Progression-free survival was significantly longer with autologous than with de-T allogeneic transplantation, but there was no significant difference in disease recurrence or mortality.
(ii) Reduced-dose pretreatment regimen (RIC) for allogeneic transplantation
Reduced pretreatment dose is mainly to reduce the high mortality rate associated with clearing regimens while exerting the GVL effect of allogeneic transplantation. The results of the studies confirm that RIC regimens do reduce mortality, expand the age range of transplantation, and benefit from the GVL effect. Patients in these studies were often multi-treated and drug-resistant patients, but nevertheless achieved a high CR rate after transplantation. The use of immunosuppressive drugs before and after transplantation is being explored to achieve a state of complete donor cell chimerism. Although the reduced-dose pretreatment regimen showed a significant reduction in early pathogenicity and lethality, the long-term efficacy needs to be further observed.
When comparing 73 patients transplanted on the reduced-dose pretreatment regimen with 82 patients registered in the European bone marrow transplant registry who underwent clear-cut transplantation during the same period, patients transplanted on the RIC regimen had significantly lower treatment-related mortality but increased relapse rates. Overall survival and disease-free survival rates were not statistically different between the two groups.
Sibling (44) and unrelated (20) donor allogeneic transplants were performed at the Fred Hutchinson Cancer Center in 64 patients with slow gonorrhea using a reduced-dose pretreatment regimen. Results showed a median age of 56 years (44-69 years), the vast majority of patients were fludarabine-resistant, and the 100-day treatment-related mortality rate was 11% and the 2-year treatment-related mortality rate was 22%, primarily due to GVHD. at a median 24-month follow-up, 39 patients were alive and 25 patients were in CR status. The two-year overall survival rate was 60% and the disease-free survival rate was 52%. Although unrelated donor transplant patients had somewhat more complications, they had a higher CR rate and a lower recurrence rate due to the GVL effect. Recent results show a 5-year disease-free progression rate of 39% and an overall survival rate of 50%.
The addition of alemtuzumab to the pretreatment regimen may reduce the occurrence of GVHD and thus TRM, however, there is a concomitant slow post-transplant hematopoietic reconstitution, increased risk of infection, and diminished GVL effect. This can be compensated by early donor lymphocyte infusion. In a study conducted at the UK Bone Marrow Transplantation Centre, using alemtuzumab in combination with fludarabine and marfalan as a pretreatment regimen, 41 patients were included in the study, including 24 sibling allografts and 17 unrelated donor transplants (4 incomplete), with 100% of chemotherapy-sensitive patients and 86% of chemotherapy-resistant patients achieving complete or partial remission. 2-year TRM rate 26% , OS 51%, relapse rate 29%. acute GVHD in 17 patients (41%) and chronic GVHD in 13 patients (33%). treatment-related deaths were mainly due to fungal and viral infections. In this study, a poor prognosis was found for patients in the fludarabine-resistant group, with an overall survival rate of only 31% at 2 years.
(iii) European bone marrow transplantation treatment guidelines
The EBMT establishes indications for slow gonorrhea allogeneic transplantation. The guidelines state that there is evidence that allogeneic stem cell transplantation is effective in the treatment of C. diff, especially for those patients at high risk. The specific high-risk factors are still not fully understood, but transplantation should be preferred after first remission in patients with P53 deletions or mutations. The status of IgVH status and cytogenetic abnormalities in disease prognosis is currently being evaluated to clarify whether they can benefit by transplantation in first remission. the EBMT working group reached consensus that for young patients who do not achieve CR or who progress within 12 months after nucleoside analogue therapy, and who have been treated with combination chemotherapy or autologous transplantation containing a nucleoside analogue regimen Patients who are effective but relapse within 24 months are indications for allogeneic transplantation.
Patients with relapsed chronic gonorrhea should be enrolled in clinical trials whenever possible. The choice of regimen should take into account several factors: type and number of previous treatment regimens, genetic risk, age, and general physical condition. Patients with early relapse after application of standard FC regimens may be treated with immunochemotherapy (e.g. FCR, BR, FA, FCA) or with alemtuzumab alone. A salvage regimen containing alemtuzumab may be considered for patients with refractory LHC (not responding to first-line therapy) or relapsing LHC with P53 mutations or deletions. Allogeneic transplantation should be considered as the next treatment for young and generally well-reformed patients with refractory relapses, patients with high-risk factors, and patients with P53 gene deletions or mutations. In particular, for patients with P53 deletion or mutation, no treatment option other than transplantation has so far been able to achieve sustained remission. Reduced-dose fludarabine or FC regimens, bendamustine, or CHOP regimens may be used for older patients who relapse after treatment with benzodiazepine. Monotherapy or new drug therapy such as ranidomide may also be considered.
VII. Outlook
In recent years, there have been tremendous advances in the first-line and salvage treatment of slow gonorrhea, and further improvements will be made in the near future. For example, today’s phase III clinical trials suggest that immunochemotherapy is superior to the current standard first-line treatment. Standard first-line treatment regimens for high-risk patients and patients with poor general condition remain to be improved. The role of autologous transplantation in the treatment of chronic gonorrhea remains unclear and is not listed in the guidelines for conventional treatment. Clinical trials have shown that autologous transplantation does not alter the poor prognosis in high-risk patients, and allogeneic transplantation should be considered in this group of patients. Clear myeloablative pretreatment regimens have not shown any advantage in autologous transplantation, and therefore, the main research focus is now on non-clear myeloablative pretreatment regimens for allogeneic transplantation.
Although the initial results are encouraging, it is not known whether allogeneic transplantation performed by RIC will result in long-term survival of CLL patients because the observation period is still short. In the treatment of patients with CLL, it is important to fully weigh whether the patient’s choice of transplantation regimen will provide the greatest benefit, rather than simply an increased risk of treatment. New drugs for slow gonorrhea are still being developed. The latest findings are encouraging, and ranidomide, monoclonal antibodies, or gene therapy are all promising new approaches to treating C. diff.