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What are the treatment methods of acute lymphoblastic leukemia?
(1) treatment

The treatment principle of ALL is the same as AML, which can be divided into two stages: induced remission and post-remission treatment, with more emphasis on the prevention and treatment of CNS-L. ALL is a heterogeneous disease with many subtypes, which should be treated differently according to different subtypes. Generally, children with ALL are divided into low risk group, standard risk group and high risk group. Adult patients have the characteristics of standard risk or high risk, the only exception is B-ALL, which needs special treatment. Many medical centers believe that infant ALL is a special subtype, which is different from the treatment of children.

1. Inducing remission Like AML, the primary purpose of all patients' treatment is to induce complete remission (CR) and restore normal hematopoietic function. The concept of "molecular" or "immune" remission (the number of leukemia cells is less than110000) is replacing the traditional concept of remission that only depends on the original cell morphological standard. Vincristine (VCR), glucocorticoids, L-asparaginase (L-ASP) and anthracycline antibiotics are the basic treatment methods to induce remission. With the improvement of chemotherapy and supportive treatment, the CR rate of AALL in children can reach 97% ~ 99%, and that in adults can reach 70% ~ 90%. In all children, the CR rate of VP regimen (weekly 1 vincristine, daily 1 prednisone) can reach 80% ~ 90%. When asparaginase and an anthracycline were added, the CR rate could reach 95% and the long-term survival rate was significantly improved. The adult CR rate of VP regimen is 36% ~ 67%, and the general remission time is only 3 ~ 7 months. Different from some subtypes of ALL in children, adult ALL needs an anthracycline, and the CR rate can be increased to 70% ~ 85% without increasing toxicity and prolonging the average remission time. In adult research, L-ASP can't improve the CR rate, but it can help to improve the disease-free survival rate (DFS). Prednisone is the most commonly used glucocorticoid. Dexamethasone (Dexamethasone) has strong penetrating ability to cerebrospinal fluid and long half-life, and is used for induction and maintenance therapy. It is more effective than prednisone in controlling the whole body and asparaginase in all children. Among different anthracycline drugs, daunorubicin (DNR), adriamycin (adriamycin) and mitoxantrone (Mit) have not been proved to be superior, but daunorubicin is the most widely used. Table 9 summarizes the schemes and results of induced remission and intensive maintenance treatment in some research centers in recent years.

Theoretically, stronger induction remission therapy can reduce the leukemia load more quickly and thoroughly, which can prevent the generation of drug-resistant cells. Some scholars use more drugs for strong induction as a method to improve CR.

2. Support treatment All patients are often accompanied by a series of complications such as infection, bleeding and hyperuricemia, and active and effective treatment should be carried out before chemotherapy.

(1) Anti-infection: Infection is the main problem in the treatment of most ALL patients. Because all patients are often accompanied by agranulocytosis when they are diagnosed, and their own immune function is disordered or their mucosa is damaged, they are easy to be complicated with infection. If it is not controlled before chemotherapy, the further decline of bone marrow suppression and immune function after chemotherapy may lead to the spread and aggravation of infection and even lead to premature death of patients. For patients with severe infection, empirical anti-infection treatment should be given before the results of various pathogen cultures come out, and attention should be paid to preventing the infection of other conditional pathogens. For patients with decreased humoral immunity, large doses of human immunoglobulin can be injected intravenously.

(2) Hemostasis: For patients with massive hemorrhage, we should not only pay attention to the number of platelets, but also pay attention to the detection of coagulation and fibrinogen. DIC patients should be treated with heparin calcium as soon as possible. Because asparaginase can reduce fibrinogen, patients treated with asparaginase should raise the fibrinogen level to near normal level before taking the drug.

(3) Alkaline urine: Hyperuricemia nephropathy is a common complication before and during chemotherapy of ALL. If it is not handled properly, it will easily lead to acute renal failure. Therefore, patients with hyperuricemia and leukocytosis should take allopurinol (300 ~ 600 mg/d) orally before chemotherapy, and at the same time alkalize urine. Patients with normal cardiac function should be given enough hydration to keep the urine volume at 65438.

(4) Leukopenia: For all patients with high white blood cell count (greater than 100× 109/L), the white blood cell count should be reduced to below 50× 109/L before routine chemotherapy. Leucocyte apheresis is commonly used, but it should be combined with low dose ETX, otherwise some patients will have pulmonary embolism and cerebral embolism due to the sharp increase of leukocyte count after separation. If there is no condition for leucocyte apheresis, for B-ALL, cyclophosphamide 200mg can be given intravenously, 1 time, 3-5 days a day, and prednisone 60mg for 5 days. For other subtypes of ALL, vincristine 0.75mg/m2 1 time and prednisone 30 mg/(m2 d) for 7 days can be considered as a mild treatment to reduce the white blood cell count.

(5) Correcting anemia: For patients with severe anemia symptoms, hematocrit cells can be infused to improve Hb, improve the body's hypoxia and improve disease resistance. For patients with anemia and high white blood cell count, the white blood cell count should be reduced before blood transfusion, otherwise embolism may occur after red blood cell transfusion.

3. Chemotherapy for adult ALL emphasizes high-dose multi-drug combination chemotherapy, which firstly induces remission, followed by preventive treatment of extramedullary infiltration such as central nervous system leukemia, and consolidated intensive treatment after complete remission. Maintenance treatment should be carried out in the interval of intensive treatment, and the total treatment time is 2 ~ 3 years.

(1) Induced remission: In 1960s and early 1970s, it was confirmed that many drugs including vincristine, prednisone, daunorubicin, asparaginase and adriamycin were effective for adult ALL. The complete remission rate of single dose therapy is 25% ~ 50%, and the combined application of vincristine and prednisone (VP regimen) in adults can increase the remission rate to 10%. However, it is still significantly lower than the complete remission rate of 70% ~ 90% in children. It has been proved that if anthracyclines and/or asparaginase are added to the VP scheme, the CR rate can be increased to 70% ~ 85%. Commonly used induced mitigation schemes are as follows:

①DVLP regimen: daunorubicin 30 ~ 40 mg/m2, intravenous injection 1 ~ 3 days, 15 ~ 17 days; Vincristine 1.5mg/m2, intravenously 1 8, 15, 22 days; Prednisone 40 ~ 60 mg/m2, oral 1 ~ 14 days, gradually reduced from 15 days to the 28th day; L-ASP6000U/m2, intravenous injection 19 ~ 28 days. This scheme takes 4 weeks as a course of treatment. At present, all the data show that the CR rate is 66% ~ 94% after 1 ~ 2 courses of treatment, and it is also the most commonly used effective induction scheme.

②DVCF regimen: The DVP regimen was given cyclophosphamide intravenously on 1 and 15 days without asparaginase. The Beijing Leukemia Cooperative Group used this regimen to treat adult ALL, and the CR rate was 90%.

③ induction therapy with high dose of cytarabine: 199 1 year Arlin and others used high dose of cytarabine (HdAra-C3g/m2×5 days) combined with mitoxantrone (6 ~ 10 mg/d× 2 days) and vincristine (1year). Kloc-0/ time /d×7 days) in the treatment of cytarabine combined with other chemotherapy drugs in the treatment of adult ALL showed that HdAra-C was mainly suitable for high-risk group ALL, but HdAra-C was not recommended for low-risk group ALL in inducing remission.

④ C.A.Linker of California, USA, proposed a holistic treatment plan for all. After 8 1 patient observation, the CR rate reached 94%, and the curative effect was not affected by the standard risk and high-risk population. It is the best scheme with the highest CR rate at present, which can prolong the disease-free survival of patients. See table 10 for details.

⑤Arlin et al. treated 10 adult ALL with high dose of mitoxantrone (2 ~ 37.5 mg/m2) × 2 days or (4 ~ 80 mg/m2) × 1 day, and all of them got CR, of which 2 cases were PhALL. See table 1 1 for commonly used ALL-induced remission schemes.

(2) Consolidation and intensive treatment: After induction and remission treatment, patients with acute leukemia still have 109 leukemia cells when reaching CR. Therefore, in order to prevent recurrence and prolong the remission period, in recent years, consolidation and intensive treatment have achieved remarkable results in the treatment of adult ALL. It is generally believed that it must be consolidated and strengthened immediately after remission. The general principle is basically to adopt multi-drug combination, alternating sequence, large dose and prevention and treatment of central nervous system leukemia.

1989 The National Leukemia Symposium held in Guiyang suggested that six courses of intensive treatment should be started 2 weeks after the DVCP regimen induced remission, with an interval of 2-3 weeks for each course. 1 and four courses of treatment are the same as the induction scheme, the second and fifth courses are EA scheme (VP 1675mg/m2, 1-3 days, cytarabine 100 ~ 150mg/m2), and the third and sixth courses of treatment.

High-dose cytarabine or other chemotherapy drugs are also used for consolidation treatment of patients with acute lymphoblastic leukemia, with moderate to large doses. The general usage of cytarabine is: cytarabine 1 ~ 3g/m2, every 1 2h 1 time, continuous drip, 3 ~ 6 days for1course of treatment.

There are many studies on intensive treatment of high-dose cytarabine, but the most reasonable dose is not clear. Although it is not clear which subtype can benefit from it, it has a good effect in children's B-ALL, with DFS greater than 80% and adult's pre-ball DFS 50% ~ 60%. For other high-risk adults, the value of high-dose cytarabine needs to be studied. In a multicenter study in Germany (03/87), a high dose of cytarabine 3g/m2 (age

Peking Union Medical College Hospital adopts the following three schemes for sequential treatment: (1)VDLP or VDCP;; (2)EA: etoposide100 mg/(m2 d), intravenous injection 1 ~ 7 days, cytarabine100 ~150mg/(m2 d), intravenous injection1. (3)HD-MTX, methotrexate 1 ~1.5g/(m2 d), only1day. Each course of treatment is 2 ~ 3 weeks apart, with a total of 3 courses.

Medium-dose and high-dose methotrexate alone or in combination with other chemotherapy drugs are also used for the consolidation and intensive treatment of adult ALL. Its application method is 0.5 ~ 3g/m2, continuous intravenous drip for 24 hours, and tetrahydrofolate is given for rescue at the end of 12h. The dose is 10% ~ 15% of methotrexate. However, it should be noted that high-dose methotrexate has an effect on B cell line acute lymphoblastic leukemia.

Allogeneic (Ailo) or autologous hematopoietic stem cell transplantation (Auto-SCT) is also an intensive therapy. It is generally believed that early reinforcement of all in adults can effectively prolong remission or prevent recurrence. In the MRC randomized study, patients who received early and late enhancement had a lower risk of recurrence. Several non-randomized studies also strongly show the benefits of intensive treatment, especially for young patients who have not received intensive treatment. Although in the GIMEMA randomized study, two courses of intensive treatment did not show advantages over conventional maintenance treatment, intensive treatment is now a part of almost ALL adult ALL treatment.

A multicenter trial in Germany added teniposide and cytarabine to consolidation therapy, and the 2-year CR rate was 40%. This scheme is especially effective for patients with empty cell ALL.

The main side effects of consolidation and intensive therapy are bone marrow suppression, neutropenia and even agranulocytosis, leading to serious infection and sepsis, and the mortality rate can reach 10%. Especially the elderly, the mortality rate is higher; Strong symptomatic and supportive treatment must be given at the same time.

(3) Maintenance treatment: There is no uniform method for maintenance treatment of adult ALL. However, some scholars found that maintenance treatment made the white blood cell count lower than 3.5× 109/L, and the risk of recurrence was lower than that of patients with high white blood cell count. Low cumulative dose of chemotherapy is also related to high recurrence rate. At present, thiopurine and methotrexate are commonly used drugs, followed by cyclophosphamide, cytarabine, vincristine and prednisone. These drugs can be used continuously as a single drug, or they can be treated with multiple drugs in turn. The commonly used methods are thiopurine 75mg/m2 orally, once a day/kloc-0, and methotrexate 20mg/m2 orally, once a week/kloc-0. How long does it take to maintain treatment?

Recent studies show that the dose intensity of thiopurine is the most important drug factor affecting the therapeutic effect, and it is better to take it at night, so it is best to give it once. Anti-metabolic therapy should not stop just because of abnormal liver function, because this abnormal liver function is tolerable and reversible. Intermittent addition of VP can improve the effect of maintenance therapy based on antimetabolites.

Long-term maintenance treatment will increase the mortality rate in remission, which cannot be completely avoided by current treatment methods. Some studies believe that the improvement of the overall survival tends to increase the intensity of treatment rather than prolong the treatment time, so at present, more attention is paid to maintaining the periodic strengthening of treatment, that is, 1 ~ 2 courses of drugs with the same initial remission intensity or a scheme with sufficient intensity to make the newly treated all patients CR. Re-induction therapy may be more effective in preventing recurrence. In the study of CCG, this treatment significantly reduced the mortality of recurrence or leukemia, improved OS, and increased the long-term DFS by about 4%. Alternating the use of non-cross-resistant drugs during maintenance treatment further improves the prognosis of standard risk or high risk. However, the GIMEMA study in Italy shows that after early and sufficient intensive treatment, maintaining the intensity of treatment has no effect on the survival rate.

Now more emphasis is placed on individualized treatment, that is, making treatment strategies according to risk factors and adopting different treatment methods for patients with different risk factors. The proliferation and differentiation potential of residual leukemia cells is another important factor to guide maintenance treatment. For example, mature B-ALL, due to rapid proliferation, short-term treatment has been very effective.

But for cells with low proliferation potential, long-term treatment may be needed. The application of molecular biology techniques, such as PCR, may help to clarify this problem. Once the patient-specific clonal changes are determined, the intensity and duration of treatment can be guided according to the degree of residual diseases.

The routine maintenance treatment in Peking Union Medical College Hospital was carried out for 2 years, combined with chemotherapy every 2 months 1 year, and combined with chemotherapy every 3 months in the second year. The scheme is as follows: ①VDCP: the same as induction remission therapy, but the time is shortened to 2 weeks; ②EA: The above two schemes are carried out alternately. When the total amount of daunorubicin reaches 500mg/m2, it is replaced by mitoxantrone or acridine. During the intermission of combined chemotherapy, the following drugs were taken orally in turn every week: thioguanine or thioguanine in 1 week100m/(m2 d); In the second week, methotrexate 1 ~ 4 days1.5 mg/(m2 d); Etoposide 75 mg/(m2 d)1~ 5 days in the third week.

4. A large number of data of hematopoietic stem cell transplantation in recent years show that the 5-year disease-free survival rate of adult ALL is still below 20%, and the long-term prognosis of adult ALL is worse than that of ALL due to extramedullary recurrence and infiltration. Therefore, most scholars believe that adult ALL patients should actively consider hematopoietic stem cell transplantation after the first CR.

5. Prevention and treatment of extramedullary leukemia Because of the special physiological structure of the central nervous system (CNS), testis, ovary and orbit, chemotherapy drugs can not reach effective killing concentration in these parts during routine chemotherapy, which is the main reason for leukemia recurrence. Therefore, prevention and treatment of extramedullary leukemia is one of the important links for leukemia patients to continuously relieve, avoid recurrence and even cure.

The incidence of CNSL and testicular leukemia in adult ALL patients is lower than that in children, and the incidence of meningeal leukemia is lower than that of 10% at the initial treatment. However, if the preventive measures of central nervous system are not taken, more than 30% of adult ALL can develop into CNSL. In particular, the prevention and treatment of CNSL should be paid attention to in patients with elevated peripheral white blood cells, elevated B cell ALL and elevated blood lactate dehydrogenase and alkaline phosphatase activities. At present, most scholars advocate that the prevention and treatment of CNSL should start as soon as possible after the patient reaches complete remission. The main methods are as follows: ① intrathecal chemotherapy, commonly used drugs are methotrexate 8 ~ 12 mg/(m2 times) combined with dexamethasone (5mg/ time), L ~ 2 times a week, 4 ~ 6 times in a row, and then injected 1 time every 4 ~ 6 weeks, generally maintaining L ~ 1 time. Some scholars also use harringtonine or homoharringtonine for intrathecal injection, but few cases have been reported and need further verification. ② Radiotherapy, the whole skull plus the whole spinal cord is feasible, which should include the whole skull (the lower boundary is 0.5 ~ 1.0 cm below the skull base bone line) and the spinal cord (the upper boundary is connected with the lower boundary of the whole skull irradiation field, and the lower boundary is to the lower edge of the second sacral vertebra); It is also feasible to expand radiotherapy. In addition to the whole skull and spinal cord mentioned above, the irradiation range also includes liver, spleen, kidney, thymus and gonad, because these organs are easy to hide leukemia cells; ③ Systemic chemotherapy. At present, medium and large doses of methotrexate are recommended. Some scholars also recommend high-dose cytarabine, but the effect of high-dose cytarabine on CNSL has been further confirmed: ④ Whole skull radiotherapy plus intrathecal injection of methotrexate or cytarabine, that is, intrathecal injection of chemotherapy drugs instead of whole spinal cord radiotherapy; Intrathecal injection 1 day or 1 week before whole skull radiotherapy, and intrathecal injection 1 ~ 2 times a week, * * * 4 ~ 6 times.

For the prevention and treatment of testicular leukemia, local radiotherapy combined with high-dose systemic chemotherapy is also emphasized, while for the prevention and treatment of ovarian leukemia, in addition to the above methods, surgical resection of the ovary can also be considered.

6. Treatment of refractory and recurrent adult acute lymphoblastic leukemia

(1) recurrence can be diagnosed as one of the following criteria: ① bone marrow primordial cells (type ⅰ+ⅱ) or primitive monocytes or primitive lymphocytes+lymphoblasts >: 5%, but

(2) The concept of refractory leukemia: ① Newly treated patients who have not received remission after two courses of standard chemotherapy; ② Recurrence within 6 months after Cr/Kloc-0 (called early recurrence); ③ Patients who relapsed 6 months after CR/KLOC-0, but did not get remission after standard chemotherapy (called late recurrence); ④ Recurrence 2 times or more.

(3) Treatment: First, consider choosing new anticancer drugs, such as teniposide, etoposide, acridine, idarubicin, Acla, etc., and use them in combination with other anticancer drugs to improve the curative effect; Secondly, we can consider using medium and high doses of cytarabine or methotrexate for treatment. For such patients who reach CR again, hematopoietic stem cell transplantation should be carried out as soon as possible if conditions permit. In addition, drug sensitivity test and P 170 test should be carried out simultaneously for such patients. For patients with positive P 170, cyclosporine A, which is recognized to be effective in reversing the drug resistance of leukemia cells, can be used in combination with chemotherapy to maximize the patient's CR again.

7. The treatment standard is the same as acute myeloid leukemia.

(2) Prognosis

Acute leukemia is a heterogeneous disease, and its prognosis is not only affected by treatment, but also the different biological characteristics of patients and malignant cells (most of which can be found by clinical and laboratory tests at the initial diagnosis) are important factors to determine different curative effects. Therefore, analyzing the clinical and experimental indexes of newly diagnosed patients can be used to estimate the prognosis (remission rate, remission period and survival time, etc.). ) and develop more targeted different treatment programs to improve the curative effect. There are many prognostic factors related to ALL. The author is limited to observing the number of cases, the length of observation, the non-randomness of case collection, the inconsistency of statistical treatment methods, and the inconsistency of treatment plans and treatment intensity, so the prognostic factors proposed are not completely consistent. At present, the recognized prognostic factors are as follows.

1. Age is one of the main prognostic factors. The onset age is 1 ~ 10 years old, and the prognosis is the best, <115 = ""25 = ""92 = ""25 = ""60 = ""77 = ""> 55% at the age of 60), the remission period and survival period were obviously shortened in turn. The poor prognosis of< 1 year-old or adults is also due to other high-risk factors, such as high white blood cell count, L2 type, extramedullary and central nervous system infiltration, non-diploid karyotype, and poor chromosome translocation (1 1G203 abnormality involves infant MLL locus and adult Ph).

2. White blood cell count is the most important determinant of remission rate and remission survival time in all age groups. At the time of diagnosis, the number of white blood cells and primitive cells was negatively correlated with the remission time, and the ratio of white blood cells 100× 109/L was even worse. When white blood cells are high, there are more extramedullary infiltration, which is easy to cause recurrence of bone marrow, central nervous system and testis. At present, it is considered that high leukocyte (>: 30× 109/L) is the main adverse prognostic factor of B-ALL. Long-term remission is rare when treated with standard regimen, but it seems to have little effect on T-ALL.

3. The duration of remission has important and independent prognostic significance. Patients who achieve complete remission (CR) within/0/4 days after induction therapy are more likely to get long-term remission. Those who gradually reach CR after 4 ~ 6 weeks of treatment are prone to produce drug-resistant clones, with high recurrence rate and generally short CR period, because the load of leukemia cells in the body cannot be reduced quickly and effectively during the treatment.

4. Patients with significantly increased number of white blood cells infiltrated outside the marrow are often accompanied by obvious infiltration outside the marrow, both of which represent the high load of leukemia cells in the body, so they have similar prognostic significance. Significant enlargement of liver, spleen and lymph nodes is not conducive to alleviating survival, but mild and moderate enlargement does not hinder prognosis; Mediastinal mass is an obvious bad feature in diagnosis, but patients with mediastinal mass often see other high-risk factors (old age, high white blood cell count, splenomegaly, Ph and so on). ) is not an independent prognostic factor. Whether in children or adults, CNSL appears at the initial diagnosis, usually with low CR rate, high recurrence rate and short survival period.

Prognostic value of 5.5. FAB subtype is controversial. It is generally believed that the prognosis of children's L 1 is better than that of L2 type, and adults' L 1 is no different from L2 type, while L3 type is not easy to relieve and has a short survival time. However, in recent years, short-term treatment has significantly improved the actual results.

6. Immunosubtypes Due to the update of treatment strategies and the application of intensive chemotherapy, the prognostic significance of all immunophenotypes has also changed greatly in recent years.

Early pre-B-ALL accounts for about 70% of all in children and 50% of all in adults. Patients of all age groups of this immune subtype usually have a good prognosis. Although CD 10 is shown in most early pre-B-ALL, its actual prognosis depends on whether it is accompanied by Ph or expresses BCR/ABL gene fusion, and CD 10 seems to have no independent prognostic significance.

Pre-B-ALL accounts for 5% ~ 20% of all/kloc-0. Compared with early pre-B-ALL, the former has higher risk of bone marrow and central nervous system recurrence and shorter survival time. 20% ~ 30% of pre-B-ALL has T (1; 19) abnormality and Cyμ are the main determinants of poor prognosis of pre-B-ALL. On the other hand, there is no t (1; 19) has a good survival rate.

Mature B-ALL is not common, only accounts for ALL.

T-ALL accounts for all 15% ~ 20%. At the initial diagnosis, white blood cells are often high, and the liver, spleen and lymph nodes are obviously enlarged. 50% ~ 60% patients have mediastinal masses, and the incidence of CNSL is high. These are the characteristics of poor prognosis. T-ALL has a low CR rate and poor survival rate for conventional chemotherapy, but since the new intensive treatment, the remission rate and survival rate have been significantly improved, and the curative effect even exceeds that of all of any other immune subtype. T-ALL has become an important symbol of good prognosis.

5% ~ 10% of children and 10% ~ 20% of adults expressed myeloid antigens such as CD 13 and CD33, followed by CD 14 and CD 15. Previously, it was thought that all patients with positive myeloid antigens had poor remission survival. Now it is considered that all * * * co-expressed lymphocyte lines and myeloid antigens neither affect CR rate nor hinder remission survival time.

In addition, some people think that the positive expression of CD34 has an independent good effect on the prognosis of B-ALL, but it does not affect the prognosis of T-ALL.

7. The changes of chromosome number and structure marked by cytogenetics have important independent prognostic significance. Whether children or adults, high diploid group ⅱ (chromosome >; 50, more common in children) than diploid and pseudodiploid (more common in adults), the prognosis is better and the remission survival time is longer; The prognosis of adult low diploid is very poor, but the adult high diploid group ⅰ (47 ~ 50 chromosomes) is not better than the low diploid. The prognosis of children with high diploid group ⅰ is similar to that of normal karyotype. Rare near tetraploid karyotype (82 ~ 94 chromosomes) has poor prognosis.

Chromosome translocation is the most powerful indicator of all adverse treatment results. t(9; 22)(Ph chromosome) and/or BCR-ABL positive is one of the worst prognostic factors for adult ALL, and its incidence increases with age. Although most PhALL is expected to be relieved by chemotherapy (CR rate >: 60%), the remission time is mostly short (5 ~ 10 months). At present, there is no report of long-term survival only by chemotherapy, so bone marrow transplantation (BMT) is the indication.

1 1q23 is abnormal, especially t (4; 1 1)(q 2 1; Q23) is the most common cytogenetic abnormality in all infants, especially in adults and children >: 1 year. t(4; 1 1) translocation and MLL gene rearrangement are related to the poor prognosis of ALL, and most patients are difficult to get remission. A few CR patients often relapse within 1 year, so intensive chemotherapy or BMT should be chosen as soon as possible. t( 1 1; 19) and t (4; 1 1).

T( 1, 19) and Cyμ were found in 25% pre-B-ALL, with high treatment failure rate and short survival period.

t(8; 14) and its variant t (2; 8)、t(8; 22) is the chromosome marker of mature B-ALL, mainly in L3(Burkitt) type. In the past, conventional chemotherapy had low CR rate and short survival period, and the prognosis was obviously improved after new treatment. t( 12; 2 1) is more common in children and is a good prognostic factor. Chromosome translocation involving14q113, such as t (10; 14)t( 1 1; 14) is more common in T-ALL, and the prognosis of conventional chemotherapy is much better.

8. Other factors with poor prognosis are generally poor, male, hemoglobin > at onset; 1 10g/L (indicating that the proliferation rate of leukemia cells is high, and the disease symptoms have appeared before anemia), platelets.

To evaluate the influence of prognostic factors on the prognosis of the disease, we should consider: ① The prognostic factors of leukemia are interrelated and influence each other, and the prognosis of each patient is the result of multiple factors; ② The influence of different prognostic factors on the prognosis of leukemia is unbalanced. Some factors have relatively great influence on prognosis (as far as ALL is concerned, age, white blood cell count, remission time, immunophenotype and cytogenetic abnormality are the most important prognostic factors), while others have relatively little influence; ③ Patients with multiple high-risk factors may have worse prognosis than patients with a single high-risk factor. At present, multivariate regression analysis and other methods are more helpful to objectively and truly evaluate the prognostic significance and value of different factors. Finally, all prognostic factors are not static. With the progress of treatment methods and in-depth research, some previously confirmed factors will gradually lose their prognostic significance, and new and more important prognostic factors (such as new molecular markers of leukemia) will be discovered continuously.