Keywords: leukemia treatment
For the past 20 years, due to emerging new anti-leukemia drug new chemotherapy treatment continue to improve, ALL prognosis improved significantly. Modern treatment is not simply to obtain relief, but to fight for the long-term survival, and ultimately a cure, and high quality of life.
1. Combined with chemotherapy in leukemia treatment and always implement the treatment. Its purpose is to try to kill the leukemia cells, remove the body of minimal residual leukemia cells and prevent the formation of drug-resistant restore bone marrow function, as soon as possible to achieve complete remission, to minimize the damage to normal tissue, reduce late sequelae of treatment.
Leukemia remission criteria:
(1) complete remission (CR) ① The clinical without anemia, bleeding, infection and leukemia cell infiltration performance; ② blood as hemoglobin> 90g / L, white blood cells normal or reduce, classification no naive cells, platelets> 100 × 109 / L; ③ The bone marrow plus as the original cells the promyelocytic stage cells (immature cells) <5% of normal red blood cell system and megakaryocytes.
(2) partial remission of clinical, blood and bone marrow in 3 1 or 2 does not reach complete remission the original standard bone marrow cells plus promyelocytic cells <20%.
(3) does not relieve clinical, blood and bone marrow, three did not reach complete remission standards, primitive cells in the bone marrow and promyelocytic cells> 20%, including ineffective.
Overview of commonly used anti-leukemia chemotherapy drug related drugs introduced see tumor articles. The use of these drugs in the treatment of leukemia, dose, indications, side effects, see the tumor articles commonly used anti-cancer drug summary table (Table 33-2).
Design chemotherapy should be considered when the cycle-specific and cycle non-specific drugs in combination, select cycle specific drugs should be used at different phases of drug compatibility.
Chemotherapy in the treatment of acute lymphoblastic divided into four parts: (1) induction therapy; ② consolidation therapy; ③ The shelter prevention; ④ maintain and enhance treatment. The correct diagnosis, classification is the basis of treatment options. The design should be based on the specific circumstances of each patient, ie, “individualized".
(1) remission induction treatment of acute leukemia in newly diagnosed when the body has more than 1012 leukemia cells. The purpose of this issue is in the short term, rapid and massive kill leukemia cells to restore the Bone Marrow normal hematopoietic function and organ function. Childhood ALL remission induction to the VP program (VCR + Pred) CR rate of 95 percent. Application weaker programs, the more residual leukemic cells in the body, and easy to form a multi-drug resistance, and thus easy to relapse. Many studies have confirmed that the leukemia treatment lies in an early stage. Therefore advocate using strongly in the treatment of early, high-dose, joint programs in the short term to achieve CR kill leukemia cells, reducing the number of minimal residual leukemia cells to prevent drug resistance formation.
① standard-risk ALL: the program ① The VCLP: VCR every 1.5 to 2mg/m2 intravenous injection, once a week for a total of 4 times; CTX600 800mg/m2 in the first day of treatment, intravenous; Pred40 ~~ 60mg / (m2 · d), orally, for 4 weeks; L-Asp10 000u/m2 intravenous or intramuscular injection, in the treatment of second or three weeks, a total of 6 to 10 times. ② VDLP: CTX for DNR each time 30 ~ 40mg/m2, intravenous injection, used in conjunction with the 2nd. Other ibid. The ③ CODLP (or COALP): plus DNR VCP on the basis of every 30 to 40mg/m2, used in conjunction with the 2nd.
The application of the above program, over 95% of patients who receive at 2 to 4 weeks of treatment CR. Since the beginning of the application of 3 to 4 drugs, leukopenia easily co-infection. L-Asp role of bone marrow suppression, it is advocated in the treatment of three weeks to start the application, the better.
(2) high-risk ALL: maximize the use of intensive chemotherapy, or CR, bone marrow, central nervous system and testicular leukemia relapse rate is still high even after. Therefore must be 4 to 6 large doses of chemotherapy drugs, such as high-dose CTX, Ara-C, DNR, MTX, VM26 and or VP16, IDR, etc.. Program: ① COAP: CTX400mg/m2 intravenous injection in the treatment of 1,15 days; VCR1.5 2mg/m2, once a week, Ara-c100mg/m2 once every 12 hours, intramuscularly or intravenously, once every for 5 to 7 days, weeks 1,3; Pred60mg / (m2 · d), oral, once every four weeks. ② CODLP: CTX800 ~ 1000mg/m2, the first day of treatment intravenously; DNR every 30 to 40mg/m2 intravenous 2,3 days each time; VCR, Pred usage, ibid; 3 weeks plus L-ASP , once every 10 days, 10,000 U / (m2 · d).
Using the above programs, generally in the second weekend (a course) can be achieved CR. Such as partial remission available the original proposal and then a course of treatment. If the treatment is five days hemogram no significant improvement or 4 weeks after bone marrow does not meet the CR should change to other programs, such as VM26 and + Ara-c or IDR + Ara-c, etc..
(2) consolidation therapy through induction of remission achieved CR after two treatment courses to continue with the original induction program. Application CODP or PODP of strong program, can be given to the L-ASP10 000U / (m2 · d), intravenous or intramuscular injection, once every 10 days. Or replacement of other programs used interchangeably.
(3) shelters prevention due to the presence of the blood-brain barrier, the dose of chemotherapy drugs in general difficult by the meninges, amounting to less than effective concentration of the drug, and thus can not effectively kill leukemia cells in the central nervous system, it is prone to the central nervous system leukemia (CNSL). Similarly, because of the presence of the blood-testis barrier, combined with the low temperature of the testicular tissue, slow metabolism, easy formation of drug-resistant leukemia cells in the testis, testicular leukemia. With the the leukemia survival of the extend of CNSL was and testicular leukemia incidence gradually increased. If there will be shelter to prevent, approximately 50% of children with ALL can occur in the CR three CNSL; boy of about 10% to 15% of testicular leukemia, an important reason for relapse the shelter prevention leukemia treatment important part.
1) the prevention of central nervous system leukemia: newly diagnosed WBC> 25 x 109 / L, low platelets, B-ALL and T-ALL prone of CNSL was. High-risk group were significantly higher than the standard-risk group, and occurred earlier. Intensive chemotherapy, high-dose MTX, Ara-C and L-ASP CNSL incidence is lower.
As a violation of the central nervous system in some cases newly diagnosed, so that when the CNSL prevention from the start of treatment. The commonly used methods of prevention:
① the simple drug sheath Note: generally use MTX, AraC, DXM triple intrathecal injection, according to the children’s ventricles capacity calculation administration (Table 33-9). On the first day of treatment intrathecal injection. The pending CR intrathecal weekly time, four consecutive times, and every 8 weeks thereafter until withdrawal.
The ② cranial irradiation plus intrathecal: CR after linear accelerator or 60Co irradiation, 5 times a week for three consecutive weeks, marked-threatening high-risk patients the total were 1800cGy and 2000cGy. Intrathecal injection on the first day of the injection. During radiotherapy once a week, for a total of 4 times. Once every 3 months after radiotherapy. Remission after two years changed to once every four months. The same doses.
(3) high-dose MTX, radiotherapy and intrathecal MTX intravenously with a large dose of both prevention CNSL, but also the prevention of testicular leukemia, is currently the most widely used method. In dose MTX (each 500 ~ 1000mg/m2) ineffective, more than not using. Consolidating after treatment is completed, a high dose of MTX every time 3g/m2, intravenous injection of a total of three courses, the interval of 10 to 14 days. 1/10 the amount of intravenous injection, intravenous infusion of the remaining 9/10 the amount of uniformity within 6 hours. For the prevention of high-dose MTX toxicity, should be given hydration, alkalinization. Intake 3000ml / (m2 · d), including 5% sodium bicarbonate 80 ~~ 100ml / (m2 · d). Generally three hours before the injection of the first input of liquid containing sodium bicarbonate, alkaline urine, so the urine pH> 7.0, the proportion of <1.010. Medication begin 36 hours after leucovorin rescue every time 15mg/m2 1 intramuscular injection, administered once every 6 hours in the future, that is, once 42,48,54,60,66 hours each administration, intravenous intramuscular injection or orally. Intrathecal in after intravenous MTX2 hours once every 8 weeks thereafter intrathecal once, until the high-dose MTX after 6 months brain radiotherapy. The high dose of MTX at the same time with the VP program.
Beijing Children’s Hospital since 1987 to apply this approach to prevention of shelter, 213 cases, only two cases of CNSL. In addition, the application of high-dose Ara-C can also prevent CNSL.
Cranial irradiation affect the child’s developing nervous system, intelligence, growth and gonad development. For the majority of patients with standard risk no longer advocate the use of this method as a means of prevention CNSL.
2) prevention of testicular leukemia testicular leukemia occurred in high-risk patients. As a precautionary measure in remission after a high dose of MTX, usage, such as the aforementioned. Beijing Children’s Hospital since the application of high-dose MTX, no case of testicular leukemia.
(4) maintenance therapy with the strengthening of the treatment by the induction of remission, the body of about 108 to 1010 Trace residual leukemic cells. So when the withdrawal, quickly relapse, hence, the need to continue maintenance treatment, kill and eventually cleared MRLC maximum extent. Requires the use of several drugs to prevent resistance, alternating rotation. But it as maintenance therapy takes a long time, the intense chemotherapy causes severe bone marrow suppression, immune dysfunction and organ damage (such as liver damage), and therefore should not be used to accumulate toxic drug. In order to strengthen MRLC kill intermittently repeated the original induction program, that the “re-induction" or “strengthen and given shock therapy on a regular basis," enhanced “treatment.
Maintenance treatment program variety, the most simple and effective method is 6MP ten MTX and MTX 20mg/m2, weekly intravenous or oral; MP50 ~ 75mg / (m2 · d), oral, once every two weeks, and then the original induction program, or the COAP to strengthen one week. Monthly medication three weeks, take a week off.
Strengthening treatment differences multi Ara-C + VM26, VM26 every time 150mg/m2 that Ara-C every time 300mg/m2 shared twice, two days apart. Strengthening treatment interval generally once every three months in one year, and then gradually extended. L-ASP Clear MDR better, it can be used regularly in the maintenance phase.
Maintenance treatment should last long, there is no unified standard, mainly based on the design of chemotherapy. General for two years and a half to three and a half years. The duration of the high-risk patients may be extended. Report 3 years almost no difference in the recurrence rate of withdrawal withdrawal over three years.
(5) relapse treatment
① bone marrow relapse: bone marrow relapse prognosis and recurrence time. (Continued complete remission, CCR) continuous complete remission for more than 3 years; especially good prognosis of recurrence after stopping, approximately 80% of the patients can get a second remission, approximately 40% of patients with long-term survival. In less than 18 months of treatment relapse, the prognosis is poor. Because of multi-drug resistant (multipledrug resistance, MDR) has produced less get a second chance of remission. Even if achieved remission, most patients relapse soon.
Must be more strongly re-induction program marrow relapse, second-line chemotherapy drugs. Such as the United States the CCSG collaborative group of patients with first relapse apply VDLP program, which DNR weekly 25mg/m2, sharing four times; L-ASP10000u/m2, three times a week, a total of 12 times, 82% of patients can be get second remission. The VM26 with Ara-C and with also again remission rate of 87%. Fewer opportunities due to bone marrow relapse after chemotherapy again to obtain long-term remission, it is conditional should do a bone marrow transplant.
The ② central nervous system relapse: the CNSL patient more than half of the non-obvious symptoms, so many neglected, often in the the conventional sheath note prevention CNSL square was found. Symptoms of headache, vomiting, fatigue, and also facial paralysis, vision loss, meningeal irritation, severe can occur hemiplegia, aphasia, convulsions and coma.
In general, CNSL in remission for less than one year, and its long-term survival rate was significantly lower than late recurrence. In recent years, due to the improvement of asylum prevention, CNSL, has significantly reduced.
CNSL diagnostic criteria: ① the signs and symptoms of central nervous system (especially the signs and symptoms of increased intracranial pressure). ② cerebrospinal fluid changes: increased pressure> 0.02 kPa (200mmH2O), or 60 drops / min; white blood cell count> 0.01 x 109 / L; smears see leukemia cells; the proteins> 450mg / L, or Paneth The test was positive. (3) exclusion of other causes similar change of the central nervous system or cerebrospinal fluid.
The CNSL treatment is not uniform, the general methods include: (1) combined with intrathecal: MTX, Ara-C, DXM triple intrathecal dose prevention. First week of every two days sheath Note 1, the second week, twice a week until the CSF normal twice instead of 1,2,3,6 weeks each, once every 6 to 8 weeks thereafter. until the termination of chemotherapy. Or start every two days the intrathecal once until changed to once every 4 to 6 weeks after CSF normal. ② radiotherapy: recurrent CNSL, cranial irradiation 18 to 26Gy three weeks, four weeks after intrathecal CSF normal spinal cord radiotherapy 10 to 18 Gy. 3 intraventricular chemotherapy: Ommaya reservoir implanted intracranial directly drugs injected into the lateral ventricle, the drug is evenly distributed throughout the subarachnoid space and reduce repeated lumbar puncture. But there is a certain risk of catheter position is not easily fixed, have coinfected danger.
③ simple testicular relapse testicular relapse after more than 2 years of remission, relapse after stopping more common. Therefore can not relax on testicular examination. Clinical multi symptoms appears only scleredema. Began more than one side of enlargement, if not treated, the contralateral also can spread.
Testicular leukemia treatment for testicular radiotherapy. Side of testicular recurrence, contralateral testicular biopsy. If only one side occurred infiltration of the ipsilateral radiotherapy. Often do not reflect the entire testis due to testicular biopsy, so advocates on both sides of the testis radiotherapy at the same time, the total amount of 20 to 24 Gy. If the
Found near the site and nearby lymph nodes leukemia cell infiltration, radiotherapy should also include these sites.
Where of CNSL, or testicular leukemia relapse, with or without bone marrow relapse are systemic remission induction therapy again, otherwise easily lead to bone marrow relapse.
2. The treatment of leukemia is bone marrow transplant bone marrow transplant (bone marrowtransplantation, BMT) by implanting pluripotent stem cells, intense chemotherapy and radiotherapy have been serious damage to the bone marrow function is restored so that children with leukemia, caused by transplantation graft-versus-leukemia effect ( graft versus leukemia, GVL) elimination of chemotherapy and radiotherapy minimal residual leukemia cells (the minimal residualleukemic cell MRLC). In recent years, due to the BMT technology and continuous improvement, the transplant success rate, and has opened up a new approach for the treatment of leukemia. Combination chemotherapy of childhood ALL better first BMT treatment. But for some of the high-risk, relapsed and refractory cases, BMT is often the most effective means of treatment.